Journal of Computational Chemistry

Improvement in molecule exchange efficiency in Gibbs ensemble Monte Carlo: Development and implementation of the continuous fractional component move.

Publication Date: 2008 May 13 PMID: 18478586
Authors: Shi, W. - Maginn, E. J.
Journal: J Comput Chem

The continuous fractional component Monte Carlo (CFC MC) move (J Chem Theory Comput, 2007, 3, 1451) is extended to the Gibbs ensemble. The algorithm is validated against conventional simulations for the Lennard Jones fluid and a flexible water model. The method is also used to compute the vapor-liquid coexistence densities of a model for SO(2). The CFC molecule exchange move relies on the gradual insertion and deletion of molecules in conjunction with a self-adapting bias potential. As a result, the method does not require the formation of spontaneous voids in the dense fluid phase to be successful, leading to molecule exchange acceptance probabilities that are nearly independent of temperature. For example, over 1% of the vapor-liquid molecule exchange moves are successful for water at 280 K, whereas advanced rotational and configurational bias methods have success rates of less than 0.03%. The CFC move can be combined with other Monte Carlo moves to enable efficient simulation of dense strongly associating fluids that are to this point infeasible to model with standard methods. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Boron-doped diamond: Investigation of the stability of surface-doping versus bulk-doping using cyclic cluster model calculations.

Publication Date: 2008 May 13 PMID: 18478585
Authors: Janetzko, F. - Bredow, T. - Geudtner, G. - Koster, A. M.
Journal: J Comput Chem

Boron-doped bulk diamond and the boron-doped hydrogen terminated (001) surface of diamond were investigated using the cyclic cluster model. Structure and stability of the hydrogen-terminated (001) surface were calculated and compared with experimental and other theoretical results from the literature. Boron-doping was modeled by substitution of a carbon atom by a boron atom in different positions with increasing distance from the surface up to boron-doped bulk diamond. In agreement with experiments on nanoclusters, boron is most stable in the first surface layers. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Comparative molecular dynamics and Monte Carlo study of statistical properties for coarse-grained heteropolymers.

Publication Date: 2008 May 13 PMID: 18478584
Authors: Schluttig, J. - Bachmann, M. - Janke, W.
Journal: J Comput Chem

Employing a simple hydrophobic-polar heteropolymer model, we compare thermodynamic quantities obtained from Andersen and Nose-Hoover molecular dynamics as well as replica-exchange Monte Carlo methods. We find qualitative correspondence in the results, but serious quantitative differences using the Nose-Hoover chain thermostat. For analyzing the deviations, we study different parameterizations of the Nose-Hoover chain thermostat. Autocorrelations from molecular dynamics and Metropolis Monte Carlo runs are also investigated. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Transition metal dimers as potential molecular magnets: A challenge to computational chemistry.

Publication Date: 2008 May 13 PMID: 18478583
Authors: Fritsch, D. - Koepernik, K. - Richter, M. - Eschrig, H.
Journal: J Comput Chem

Dimers are the smallest chemical objects that show magnetic anisotropy. We focus on 3d and 4d transition metal dimers that have magnetic ground states in most cases. Some of these magnetic dimers have a considerable barrier against re-orientation of their magnetization, the so-called magnetic anisotropy energy, MAE. The height of this barrier is important for technological applications, as it determines, e.g., the stability of information stored in magnetic memory devices. It can be estimated by means of relativistic density functional calculations. Our approach is based on a full-potential local-orbital method (FPLO) in a four-component Dirac-Kohn-Sham implementation. Orbital polarization corrections to the local density approximation are employed. They are discussed in the broader context of orbital dependent density functionals. Ground state properties (spin multiplicity, bond length, harmonic vibrational frequency, spin- and orbital magnetic moment, and MAE) of the 3d and 4d transition metal dimers are evaluated and compared with available experimental and theoretical data. We find exceptionally high values of MAE, close to 0.2 eV, for four particular dimers: Fe(2), Co(2), Ni(2), and Rh(2). (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Insights on protein-DNA recognition by coarse grain modelling.

Publication Date: 2008 May 13 PMID: 18478582
Authors: Poulain, P. - Saladin, A. - Hartmann, B. - Prevost, C.
Journal: J Comput Chem

Coarse grain modelling of macromolecules is a new approach, potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein-DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein-DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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QSAR model for alignment-free prediction of human breast cancer biomarkers based on electrostatic potentials of protein pseudofolding HP-lattice networks.

Publication Date: 2008 May 13 PMID: 18478581
Authors: Vilar, S. - Gonzalez-Diaz, H. - Santana, L. - Uriarte, E.
Journal: J Comput Chem

Network theory allows relationships to be established between numerical parameters that describe the molecular structure of genes and proteins and their biological properties. These models can be considered as quantitative structure-activity relationships (QSAR) for biopolymers. The work described here concerns the first QSAR model for 122 proteins that are associated with human breast cancer (HBC), as identified experimentally by Sjoblom et al. (Science 2006, 314, 268) from over 10,000 human proteins. In this study, the 122 proteins related to HBC (HBCp) and a control group of 200 proteins that are not related to HBC (non-HBCp) were forced to fold in an HP lattice network. From these networks a series of electrostatic potential parameters (xi(k)) was calculated to describe each protein numerically. The use of xi(k) as an entry point to linear discriminant analysis led to a QSAR model to discriminate between HBCp and non-HBCp, and this model could help to predict the involvement of a certain gene and/or protein in HBC. In addition, validation procedures were carried out on the model and these included an external prediction series and evaluation of an additional series of 1000 non-HBCp. In all cases good levels of classification were obtained with values above 80%. This study represents the first example of a QSAR model for the computational chemistry inspired search of potential HBC protein biomarkers. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Alpha7 nicotinic acetylcholine receptor agonists: Prediction of their binding affinity through a molecular mechanics Poisson-Boltzmann surface area approach.

Publication Date: 2008 May 13 PMID: 18478580
Authors: Grazioso, G. - Cavalli, A. - De Amici, M. - Recanatini, M. - De Micheli, C.
Journal: J Comput Chem

A group of agonists for the alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies of binding DeltaG(bind) were calculated by applying the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approach. This method, based on molecular dynamics simulations of fully solvated protein-ligand complexes, allowed us to estimate the contribution of both polar and nonpolar terms as well as the entropy to the overall free energy of binding. The calculated results were in a good agreement with the experimentally determined DeltaG(bind) values, thereby pointing to the MM-PBSA protocol as a valuable computational tool for the rational design of specific agents targeting the neuronal alpha7 nAChR subtypes. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Structures, stabilities, electronic, and optical properties of C(64) fullerene isomers, anions (C(64) (2-) and C(64) (4-)), metallofullerene Sc(2)@C(64), and Sc(2)C(2)@C(64).

Publication Date: 2008 May 13 PMID: 18478579
Authors: Cui, Y. H. - Tian, W. Q. - Feng, J. K. - Chen, D. L.
Journal: J Comput Chem

The 3465 classical isomers of C(64) fullerene have been investigated by quantum chemical methods PM3, and the most stable isomers have been refined with HCTH/3-21G//SVWN/STO-3G, B3LYP/6-31G(d)//HCTH/3-21G, and B3LYP/6-311G(d)//B3LYP/6-31G(d) level. C(64)(D(2):0003) with the lowest e(55) (e(55) = 2), the number of pentagon-pentagon fusions, is predicted to be the most stable isomer and it is followed by the C(64)(C(s):0077) and C(64)(C(2):0103) isomers within relative energy of 20.0 kcal/mol. C(64)(D(2):0003) prevails in a wide temperature range according to energy analysis with entropy contribution at B3LYP/6-31G(d) level. The simulated IR spectra and electronic spectra help to identify different fullerene isomers. All the hexagons in the isomers with e(55) = 2 display local aromaticity. The relative stabilities of C(64) isomers change with charging in ionic states. Doping also affects the relative stabilities of fullerene isomers as demonstrated by Sc(2)@C(64)(D(2):0003) and Sc(2)@C(64)(C(s):0077). The bonding of Sc atoms with C(64) elongates the C--C bond of two adjacent pentagons and enhances the local aromaticity of the fullerene cages. Charging, doping, and derativization can be utilized to isolate C(64) isomers through differentiating the electronic and steric effects. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Roles of cations, electronegativity difference, and anionic interlayer interactions in the metallic versus nonmetallic character of Zintl phases related to arsenic.

Publication Date: 2008 May 12 PMID: 18473357
Authors: Alemany, P. - Llunell, M. - Canadell, E.
Journal: J Comput Chem

A first-principles Density Functional Theory study of several layered solids structurally related to rhombohedral arsenic has been carried out. The electronic structures of rhombohedral arsenic, CaSi(2), CaAl(2)Si(2), KSnSb, and SrSn(2)As(2) are discussed in detail, emphasizing on the origins of their metallic or nonmetallic behaviours. It is found that all of these systems are metallic except KSnSb. Electronegativity differences between the elements in the anionic sublattice and/or direct interlayer interactions play the main role in controlling the conductivity behavior. CaSi(2) exhibits a peculiar feature since the cation directly influences the conductivity but is not essential for its appearance. Cation-anion interactions are shown to have an important covalent contribution, but despite this fact and the metallic character found for most of these phases, the Zintl approach still provides a valid approximation to their electronic structure. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Photoionization cross sections of H(2) (+) and H(2) with complex Gaussian-type basis functions optimized for the frequency-dependent polarizabilities.

Publication Date: 2008 May 12 PMID: 18473327
Authors: Morita, M. - Yabushita, S.
Journal: J Comput Chem

Within the framework of the complex basis function method, the photoionization cross sections of H(2) (+) and H(2) were calculated based on the variational principle for the frequency-dependent polarizabilities. In these calculations, complex orbital exponents of Gaussian-type basis functions for the final state continuum wavefunctions were fully optimized for each photon energy with the numerical Newton-Raphson method. In most cases, the use of only one or two complex Gaussian-type basis functions was enough to obtain excellent agreement with previous high precision calculations and available experimental results. However, there were a few cases, in which the use of complex basis functions having various angular momentum quantum numbers was crucial to obtain the accurate results. The behavior of the complex orbital exponents as a function of photon energy was discussed in relation to the scaling relation and the effective charge for photoelectron. The success of this method implies the effectiveness of the optimization of orbital exponents to reduce the number of basis functions and shows the possibility to calculate photoionization cross sections of general molecules using only Gaussian-type basis functions. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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An optimized initialization algorithm to ensure accuracy in quantum Monte Carlo calculations.

Publication Date: 2008 May 12 PMID: 18473326
Authors: Fisher, D. R. - Kent, D. R. 4th - Feldmann, M. T. - Goddard, W. A. 3rd
Journal: J Comput Chem

Quantum Monte Carlo (QMC) calculations require the generation of random electronic configurations with respect to a desired probability density, usually the square of the magnitude of the wavefunction. In most cases, the Metropolis algorithm is used to generate a sequence of configurations in a Markov chain. This method has an inherent equilibration phase, during which the configurations are not representative of the desired density and must be discarded. If statistics are gathered before the walkers have equilibrated, contamination by nonequilibrated configurations can greatly reduce the accuracy of the results. Because separate Markov chains must be equilibrated for the walkers on each processor, the use of a long equilibration phase has a profoundly detrimental effect on the efficiency of large parallel calculations. The stratified atomic walker initialization (STRAW) shortens the equilibration phase of QMC calculations by generating statistically independent electronic configurations in regions of high probability density. This ensures the accuracy of calculations by avoiding contamination by nonequilibrated configurations. Shortening the length of the equilibration phase also results in significant improvements in the efficiency of parallel calculations, which reduces the total computational run time. For example, using STRAW rather than a standard initialization method in 512 processor calculations reduces the amount of time needed to calculate the energy expectation value of a trial function for a molecule of the energetic material RDX to within 0.01 au by 33%. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Structure and dynamics of phosphate ion in aqueous solution: An ab initio QMCF MD study.

Publication Date: 2008 May 12 PMID: 18473325
Authors: Pribil, A. B. - Hofer, T. S. - Randolf, B. R. - Rode, B. M.
Journal: J Comput Chem

A simulation of phosphate in aqueous solution was carried out employing the new QMCF MD approach which offers the possibility to investigate composite systems with the accuracy of a QMMM method but without the time consuming creation of solute-solvent potential functions. The data of the simulations give a clear picture of the hydration shells of the phosphate anion. The first shell consists of 13 water molecules and each oxygen of the phosphate forms in average three hydrogens bonds to different solvent molecules. Several structural parameters such as radial distribution functions and coordination number distributions allow to fully characterize the embedding of the highly charged phosphate ion in the solvent water. The dynamics of the hydration structure of phosphate are described by mean residence times of the solvent molecules in the first hydration shell and the water exchange rate. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Theoretical characterizations of HAsXH (X = N, P, As, Sb, and Bi) isomers in the singlet and triplet states.

Publication Date: 2008 May 12 PMID: 18473324
Authors: Lai, C. H. - Su, M. D.
Journal: J Comput Chem

The lowest singlet and triplet potential energy surfaces for all group 15 HAsXH (X = N, P, As, Sb, and Bi) systems have been explored through ab initio calculations. The geometries of the various isomers were determined at the QCISD/LANL2DZdp level and confirmed to be minima by vibrational analysis. In the case of nitrogen, the global minimum is found to be a triplet H(2)NAs structure. For the phosphorus case, singlet trans-HAs==PH is found to be global minima surrounded by large activation barriers, so that it should be observable. For arsenic, theoretical investigations demonstrate that the stability of HAsAsH isomers decreases in the order singlet trans-HAs==AsH > triplet H(2)AsAs > singlet cis-HAs==AsH > triplet HAsAsH > singlet H(2)AsAs. For antimony and bismuth, the theoretical findings suggest that the stability of HAsXH (X = Sb and Bi) systems decreases in the order triplet H(2)AsX approximately singlet trans-HAs==XH > singlet cis-HAs==XH > triplet HAsXH > triplet H(2)XAs > singlet H(2)AsX > singlet H(2)XAs. Our model calculations indicate that the relativistic effect on heavier group 15 elements should play an important role in determining the geometries as well as the stability of HAsXH molecules. The results obtained are in good agreement with the available experimental data and allow a number of predictions to be made. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Periodic local MP2 method for the study of electronic correlation in crystals: Theory and preliminary applications.

Publication Date: 2008 May 12 PMID: 18473323
Authors: Pisani, C. - Maschio, L. - Casassa, S. - Halo, M. - Schutz, M. - Usvyat, D.
Journal: J Comput Chem

A computational technique for solving the MP2 equations for periodic systems using a local-correlation approach and implemented in the CRYSCOR code is presented. The Hartree-Fock solution provided by the CRYSTAL program is used as a reference. The motivations for the implementation of the new code are discussed, and the techniques adopted are briefly recalled. With respect to the original formulation (Pisani et al., J Chem Phys 2005, 122, 094113), many new features have been introduced in CRYSCOR to improve its efficiency and robustness. In particular, an adaptation of the density fitting scheme to translationally periodic systems is described, based on Fourier transformation techniques. Three examples of application are provided, concerning the CO(2) crystal, proton transfer in ice XI, and the adsorption of methane on MgO (001). The results obtained with the periodic LMP2 method for these systems appear more reliable than the ones obtained using density functional theory. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Cohesive properties of CeN and LaN from first principles.

Publication Date: 2008 May 12 PMID: 18473322
Authors: Voloshina, E. - Paulus, B.
Journal: J Comput Chem

The effect of electron-correlation on the ground-state properties of CeN and LaN is studied by ab initio quantum-chemical methods. The approach which is used combines two separate steps: (1) the ground-state Hartree-Fock calculations for the crystal; (2) application of the method of increments to the studied system, which allows an expansion of bulk properties using the information from quantum-chemical calculations performed for finite clusters. As can be expected, for CeN correlation plays a significant role: with Hartree-Fock method only 49% of the experimental cohesive energy has been recovered, whereas after correlation corrections (coupled-cluster approach) the ground-state properties were found to be in good agreement with the experimental data found in literature. Thus, we obtained about 90% of the expected cohesive energy; the computed lattice constants and bulk moduli also agree well with the experimental values. For comparison, the equivalent treatment has been performed for LaN, where no f orbital is occupied. There the HF contribution to the ground-state properties is larger and hence the correlation effects weaker. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Influence of intrinsic defects on the properties of zinc oxide.

Publication Date: 2008 May 12 PMID: 18473321
Authors: Jug, K. - Tikhomirov, V. A.
Journal: J Comput Chem

The effects of oxygen vacancies and zinc interstitials on the structure and energy of zinc oxide were studied with the semiempirical MO method MSINDO. Cyclic clusters were chosen as model systems. Single and multiple removal of oxygen atoms and zinc interstitials in zinc oxide served to determine the defect formation energy and the band gap. The interaction between two and three oxygen vacancies was investigated. The vacancies cause a decrease of the band gap, which originates from an occupied defect level. This is also found for zinc interstitials under zinc rich conditions. The defect formation energy of such zinc interstitials is found to be lower than that of oxygen vacancies at 0 K but decreases for oxygen vacancies and increases for zinc interstitials with increasing temperature. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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QM/MM vibrational mode tracking.

Publication Date: 2008 May 12 PMID: 18470972
Authors: Herrmann, C. - Neugebauer, J. - Reiher, M.
Journal: J Comput Chem

Vibrational spectroscopy is a powerful tool to investigate the structure and dynamics of biomolecules. When small subsystems of large molecules such as active centers of enzymes are studied, quantum chemical calculations based on quantum mechanics/molecular mechanics (QM/MM) coupling schemes are a valuable means to interpret the spectra. The goal of this work is a methodological pilot study on how to selectively and thus efficiently extract certain vibrational information for extended molecular systems described by QM/MM methods. This is achieved by an extension of the mode tracking algorithm and a comparison with the partial Hessian diagonalization approach. After validating the methodology for the CO stretching vibration of 2-butanone and a delocalized CO stretch in acetylacetone, the stretching and bending modes of the CO ligand in CO myoglobin are tracked. Such systems represent an ideal application for mode tracking, because only a few strongly localized vibrations are sought for, while the large remainder of the molecule is of interest only as far as it affects these local vibrations. This influence is treated exactly by mode tracking. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Re-examination of structure optimization of off-lattice protein AB models by conformational space annealing.

Publication Date: 2008 May 12 PMID: 18470971
Authors: Lee, J. - Joo, K. - Kim, S. Y. - Lee, J.
Journal: J Comput Chem

The global structural optimization is carried out for off-lattice protein AB models in two and three dimensions by conformational space annealing. The models consist of hydrophobic and hydrophilic monomers in Fibonacci sequences. To accelerate the convergence, we have introduced a shift operator in the internal coordinate system, and effectively reduced the search space by forming a quotient space. With this, we significantly improve our previous results on AB models, and provide new low energy conformations. This work provides insights on exploring complicated energy landscapes by exploiting the advantages and limitations of CSA. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Bond-based 3D-chiral linear indices: Theory and QSAR applications to central chirality codification.

Publication Date: 2008 May 12 PMID: 18470969
Authors: Castillo-Garit, J. A. - Marrero-Ponce, Y. - Torrens, F. - Garcia-Domenech, R. - Romero-Zaldivar, V.
Journal: J Comput Chem

The recently introduced non-stochastic and stochastic bond-based linear indices are been generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D-chirality correction factor. These improved modified descriptors are applied to several well-known data sets to validate each one of them. Particularly, Cramer's steroid data set has become a benchmark for the assessment of novel quantitative structure activity relationship methods. This data set has been used by several researchers using 3D-QSAR approaches such as Comparative Molecular Field Analysis, Molecular Quantum Similarity Measures, Comparative Molecular Moment Analysis, E-state, Mapping Property Distributions of Molecular Surfaces, and so on. For that reason, it is selected by us for the sake of comparability. In addition, to evaluate the effectiveness of this novel approach in drug design we model the angiotensin-converting enzyme inhibitory activity of perindoprilate's sigma-stereoisomers combinatorial library, as well as codify information related to a pharmacological property highly dependent on the molecular symmetry of a set of seven pairs of chiral N-alkylated 3-(3-hydroxyphenyl)-piperidines that bind sigma-receptors. The validation of this method is achieved by comparison with earlier publications applied to the same data sets. The non-stochastic and stochastic bond-based 3D-chiral linear indices appear to provide a very interesting alternative to other more common 3D-QSAR descriptors. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Spin-orbit ab initio investigation of the photodissociation of dibromomethane in the gas and solution phases.

Publication Date: 2008 May 12 PMID: 18470968
Authors: Liu, Y. - Xiao, H. - Sun, M. - Fang, W.
Journal: J Comput Chem

A clear and reliable theoretical investigation on dibromomethane (CH(2)Br(2)) photodissociation is desired. The calculation must consider: (i) relativistic effects; (ii) the potential energy curves (PECs) of spin-orbit coupling states; (iii) geometry optimization by the method with both static and dynamic electron correlations; (iv) solvent effects on the photodissociation in the solution. All these have been considered in this study by state-of-the-art quantum chemical calculations. The experimentally observed photodissociation in the gas phase with products of spin-orbit-coupled states, Br((2)P(3/2)) and Br*((2)P(1/2)), was assigned by multi-state second order multiconfigurational perturbation theory in conjunction with spin-orbit interaction through complete active space state interaction (MS-CASPT2/CASSI-SO) PECs. The mechanisms of the experimentally observed photodissociation and photoisomerization in solvent were elucidated by the MS-CASPT2/CASSI-SO method combined with polarized continuum model of the solvent. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Improved pK(a) prediction: Combining empirical and semimicroscopic methods.

Publication Date: 2008 May 12 PMID: 18470967
Authors: Kieseritzky, G. - Knapp, E. W.
Journal: J Comput Chem

Using three different methods we tried to compute 171 experimentally known pK(a) values of ionizable residues from 15 different proteins and compared the accuracies of computed pK(a) values in terms of the root mean square deviation (RMSD) from experiment. One method is based on a continuum electrostatic model of the protein including conformational flexibility (KBPLUS). The others are empirical approaches with PROPKA deploying physically motivated energy terms with adjustable parameters and PKAcal using an empirical function with no physical basis. PROPKA reproduced the pK(a) values with highest overall accuracy. Differentiating the data set into weakly and strongly shifted experimental pK(a) values, however, we found that PROPKA's accuracy is better if the pK(a) values are weakly shifted but on equal footing with that of KBPLUS for more strongly shifted values. On the other hand, PKAcal reproduces strongly shifted pK(a) values badly but weakly shifted values with the same accuracy as PROPKA. We tested different consensus approaches combining data from all three methods to find a general procedure for most accurate pK(a) predictions. In most of the cases we found that the consensus approach reproduced experimental data with better accuracy than any of the individual methods alone. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Additive empirical force field for hexopyranose monosaccharides.

Publication Date: 2008 May 12 PMID: 18470966
Authors: Guvench, O. - Greene, S. N. - Kamath, G. - Brady, J. W. - Venable, R. M. - Pastor, R. W. - Mackerell, A. D. Jr
Journal: J Comput Chem

We present an all-atom additive empirical force field for the hexopyranose monosaccharide form of glucose and its diastereomers allose, altrose, galactose, gulose, idose, mannose, and talose. The model is developed to be consistent with the CHARMM all-atom biomolecular force fields, and the same parameters are used for all diastereomers, including both the alpha- and beta-anomers of each monosaccharide. The force field is developed in a hierarchical manner and reproduces the gas-phase and condensed-phase properties of small-molecule model compounds corresponding to fragments of pyranose monosaccharides. The resultant parameters are transferred to the full pyranose monosaccharides, and additional parameter development is done to achieve a complete hexopyranose monosaccharide force field. Parametrization target data include vibrational frequencies, crystal geometries, solute-water interaction energies, molecular volumes, heats of vaporization, and conformational energies, including those for over 1800 monosaccharide conformations at the MP2/cc-pVTZ//MP2/6-31G(d) level of theory. Although not targeted during parametrization, free energies of aqueous solvation for the model compounds compare favorably with experimental values. Also well-reproduced are monosaccharide crystal unit cell dimensions and ring pucker, densities of concentrated aqueous glucose systems, and the thermodynamic and dynamic properties of the exocyclic torsion in dilute aqueous systems. The new parameter set expands the CHARMM additive force field to allow for simulation of heterogeneous systems that include hexopyranose monosaccharides in addition to proteins, nucleic acids, and lipids. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Force field parameters for rotation around chi torsion axis in nucleic acids.

Publication Date: 2008 May 12 PMID: 18470965
Authors: Ode, H. - Matsuo, Y. - Neya, S. - Hoshino, T.
Journal: J Comput Chem

To raise the accuracy of the force field for nucleic acids, several parameters were elaborated, focusing on the rotation around chi torsion axis. The reliability of molecular dynamics (MD) simulation was significantly increased by improving the torsion parameters at C8--N9--C1'--X (X = H1', C2', O4') in A, G and those at C6--N1--C1'--X in C, T, and U. In this work, we constructed small models representing the chemical structure of A, G, C, T, and U, and estimated energy profile for chi-axis rotation by executing numerous quantum mechanical (QM) calculations. The parameters were derived by discrete Fourier transformation of the calculated QM data. A comparison in energy profile between molecular mechanical (MM) calculation and QM one shows that our presently derived parameters well reproduce the energy surface of QM calculation for all the above torsion terms. Furthermore, our parameters show a good performance in MD simulations of some nucleic acids. Hence, the present refinement of parameters will enable us to perform more accurate simulations for various types of nucleic acids. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Mechanistic studies on the formation of glycosidase-substrate and glycosidase-inhibitor covalent intermediates.

Publication Date: 2008 May 12 PMID: 18470964
Authors: Bras, N. F. - Moura-Tamames, S. A. - Fernandes, P. A. - Ramos, M. J.
Journal: J Comput Chem

Glycoside hydrolases catalyze the breaking of the glycosidic bond. This type of bond fashioned between two monosaccharides is very stable, and the polymers created are involved in multiple cellular processes, being crucial to life. In this article, computational methods were used to study the first step of the mechanism of reaction of retaining glycoside hydrolases in atomic detail. The systems modeled included a simplified reaction center and a small substrate/inhibitor. Using DFT calculations we were able to corroborate and provide molecular-level detail to the dissociative mechanism proposed in the literature. The role of the hydrogen bridge between the nucleophile and the C(2)--OH group of the ring was also investigated. Therefore, we concluded that this bridge is responsible for lowering the activation barrier by 5.1 kcal mol(-1) with functional BB1K/6-311+G(2d,2p), and the absence of the bridge explains, at least in part, the inhibitory effect of fluoro-substituted glycosides in the -2 position. The hydrogen bridge could also be involved in favoring the ring distortion verified in the transition state, and the dissociative character of the reaction mechanism. Using the NBO method, point atomic charges were calculated. In the transition state, the positive charge generated in the sugar ring is distributed nearly equally between the anomeric carbon and the ring oxygen, through a partial double bond involving the two atoms. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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The dramatic effect of NH(3) co-ligation on the FE(+)-assisted activation of carbon dioxide in the gas phase: From bare metal ions to complexes.

Publication Date: 2008 May 1 PMID: 18452127
Authors: Karipidis, P. A. - Tsipis, C. A.
Journal: J Comput Chem

The catalytic efficiency of Fe(+) ion over the CO(2) decomposition in the gas phase has been extensively investigated with the help of electronic structure calculation methods. Potential-energy profiles for the activation process Fe(+) + CO(2) --> CO + FeO(+) along two rival potential reaction paths, namely the insertion and addition pathways, originating from the end-on kappa(1)-O and kappa(2)-O,O coordination modes of CO(2) with the metal ion, respectively, have been explored by DFT calculations. For each pathway the potential energy surfaces of the high-spin sextet (S = 5/2) and the intermediate-spin quartet (S = 3/2) spin-states have been explored. The complete energy reaction profile calculated by a combination of ab initio and density functional theory (DFT) computational techniques reveals a two-state reactivity, involving two spin inversions, for the decomposition process and accounts well for the experimentally observed inertness of bare Fe(+) ions towards CO(2) activation. Furthermore, the coordination of up to three extra ancillary NH(3) ligands with the Fe(+) metal ion has been explored and the geometric and energetic reaction profiles of the CO(2) activation processes Fe(+) + n.NH(3) + CO(2) --> [Fe(NH(3))(n)(CO(2))](+) --> [Fe(NH(3))(n)(O)(CO)](+) --> CO + [Fe(O)(NH(3))(n)](+) (n = 1, 2 or 3) have thoroughly been scrutinized for both the insertion and the addition mechanisms. Inter alia, the geometries and energies of the various states of the [Fe(NH(3))(n)(CO(2))](+) and [Fe(NH(3))(n)(O)(CO)](+) complexes are explored and compared. Finally, a detailed analysis of the coordination modes of CO(2) in the cationic [Fe(NH(3))(n)(CO(2))](+) (n = 0, 1, 2 and 3) complexes is presented. (c) 2008 Wiley Periodicals, Inc.J Comput Chem, 2008.

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Hydration of ionic species studied by the reference interaction site model with a repulsive bridge correction.

Publication Date: 2008 May 1 PMID: 18452125
Authors: Chuev, G. N. - Fedorov, M. V. - Chiodo, S. - Russo, N. - Sicilia, E.
Journal: J Comput Chem

We have tested the reference interaction site model (RISM) for the case of the hypernetted chain (HNC) and the partially linearized hypernetted chain (PLHNC) closures improved by a repulsive bridge correction (RBC) for ionic hydrated species. We have analyzed the efficiency of the RISM/HNC+RBC and RISM/PLHNC+RBC techniques for decomposition of the electrostatic and the nonpolar hydration energies on the energetic and the enthalpic parts for polyatomic ions when the repulsive bridge correction is treated as a thermodynamic perturbation, and investigate the repulsive bridge effect on the electrostatic potential induced by solvent on solute atoms. For a number of univalent and bivalent atomic ions, molecular cations, and anions, the method provides hydration energies deviating only by several percents from the experimental data. In most cases, the enthalpic contributions to the free energies are also close to the experimental results. The above models are able to satisfactory predict the hydration energies as well as the electrostatic potential around the ionic species. For univalent atomic ions, they also provide qualitative estimates of the Samoilov activation energies. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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A computational study of the crystal and electronic structure of the room temperature organometallic ferromagnet V(TCNE)(2).

Publication Date: 2008 May 1 PMID: 18452124
Authors: Tchougreeff, A. L. - Dronskowski, R.
Journal: J Comput Chem

We study numerically the crystal and electronic structure of the room temperature organometallic ferromagnet of general composition V(TCNE)(x) x y solvent with x approximately 2, starting from both the experimental structure of its iron analog which results from the EXAFS experiment as well as the theoretical model structure compatible with magnetic measurements on this type of compounds. The results of the numerical study performed at the density functional level of theory show that the experimentally determined structure complies with the magnetic measurements and thus can serve as a prototype structure for the entire family of the M(TCNE)(2) organometallic magnets. Both the results of the numerical study and the magnetic experiments are interpreted using a proposed model Hamiltonian. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Desirability-based multiobjective optimization for global QSAR studies: Application to the design of novel NSAIDs with improved analgesic, antiinflammatory, and ulcerogenic profiles.

Publication Date: 2008 May 1 PMID: 18452123
Authors: Cruz-Monteagudo, M. - Borges, F. - Cordeiro, M. N.
Journal: J Comput Chem

Up to now, very few reports have been published concerning the application of multiobjective optimization (MOOP) techniques to quantitative structure-activity relationship (QSAR) studies. However, none reports the optimization of objectives related directly to the desired pharmaceutical profile of the drug. In this work, for the first time, it is proposed a MOOP method based on Derringer's desirability function that allows conducting global QSAR studies considering simultaneously the pharmacological, pharmacokinetic and toxicological profile of a set of molecule candidates. The usefulness of the method is demonstrated by applying it to the simultaneous optimization of the analgesic, antiinflammatory, and ulcerogenic properties of a library of fifteen 3-(3-methylphenyl)-2-substituted amino-3H-quinazolin-4-one compounds. The levels of the predictor variables producing concurrently the best possible compromise between these properties is found and used to design a set of new optimized drug candidates. Our results also suggest the relevant role of the bulkiness of alkyl substituents on the C-2 position of the quinazoline ring over the ulcerogenic properties for this family of compounds. Finally, and most importantly, the desirability-based MOOP method proposed is a valuable tool and shall aid in the future rational design of novel successful drugs. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Convergence of electric field and electric field gradient versus atomic basis sets in all-siliceous and Mg substituted phillipsites.

Publication Date: 2008 Apr 28 PMID: 18442085
Authors: Larin, A. V. - Sakodynskaya, I. K. - Trubnikov, D. N.
Journal: J Comput Chem

Electrostatic potential (EP), electric field (EF), and electric field gradient (EFG) values are calculated in periodic models of magnesium substituted phillipsite (MgPHI) zeolite forms using periodic DFT (PDFT) hybrid B3LYP level with fourteen different basis sets. Relative root mean square differences between the EP, EF, or EFG values estimated between different basis sets are evaluated in several spatial domains available for adsorbate molecules in the zeolite. In these areas, the EF increase in MgPHI is evaluated relative to all-siliceous PHI types. The EP is interpreted in terms of framework ionicity for MgPHI and all-siliceous PHI models. Angular Si--O--Si dependence of the EFG asymmetry at (17)O atoms in all-siliceous zeolites is discussed. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Photoionization cross sections with optimized orbital exponents within the complex basis function method.

Publication Date: 2008 Apr 28 PMID: 18442084
Authors: Morita, M. - Yabushita, S.
Journal: J Comput Chem

We show a new direction to expand the applicability of the complex basis function method for calculating photoionization cross sections through the imaginary part of the frequency-dependent polarizability. Based on the variational stability of the frequency-dependent polarizability, we made nonlinear optimizations of complex orbital exponents in basis functions representing continuum wave functions, and obtained fairly accurate results for H atom with only one or two complex basis functions particularly with dipole velocity gauge. Results were almost independent of whether Slater-type or Gaussian-type orbitals are used, implying the applicability to general many electron problems. The method was also applied to the (1)S (1s)(2) --> (1)P (1s)(1)(kp)(1) cross section of He atom and the optimized complex orbital exponents were related to those of H atom through the scaling property. The nonlinear optimizations have converged smoothly and the cross sections were in excellent agreement with experiment throughout wide photon energies, which suggest the effectiveness of the approach for many-electron systems. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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On the modeling of arginine-bound carboxylates: A case study with Pyruvate Formate-Lyase.

Publication Date: 2008 Apr 28 PMID: 18442083
Authors: Condic-Jurkic, K. - Perchyonok, V. T. - Zipse, H. - Smith, D. M.
Journal: J Comput Chem

High level ab initio and density functional calculations have been employed to determine the most appropriate manner in which to truncate an arginine-bound carboxylate motif, using the substrate mechanism of Pyruvate Formate-Lyase as a case study. The results show that, both qualitatively and quantitatively, a neutral carboxylic acid provides a more realistic approximation to the salt bridge arrangement than does a bare anionic carboxylate substituent. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Ab initio computational study of positron emission tomography ligands interacting with lipid molecule for the prediction of nonspecific binding.

Publication Date: 2008 Apr 28 PMID: 18442082
Authors: Rosso, L. - Gee, A. D. - Gould, I. R.
Journal: J Comput Chem

Nonspecific binding is a poorly understood biological phenomenon of relevance in the study of small molecules interactions in vivo and in drug development. Nonspecific binding is thought to be correlated in part to a molecule's lipophilicity, typically estimated by measuring (or calculating) octanol-water partition coefficient. This is, however, a gross simplification of a complex phenomenon. In this article, we present a computational method whose aim is to help identify positron emission tomography (PET) ligands with low nonspecific binding characteristics by investigating the molecular basis of ligand-membrane interaction. We considered a set consisting of 10 well-studied central nervous system PET radiotracers acting on a variety of molecular targets. Quantum mechanical calculations were used to estimate the strength of the interaction between each drug molecule and one phospholipid molecule commonly present in mammalian membranes. The results indicate a correlation between the computed drug-lipid interaction energy and the in vivo nonspecific distribution volume relative to the free tracer plasma concentration, calculated using standard compartmental modeling for the analysis of PET data. Significantly, the drugs whose interaction with the lipid molecule more favorably possessed, in general, a higher nonspecific binding value, whereas for the drugs taken in consideration in this study, the water-octanol partition coefficient, log P, did not show good predictive power of the nonspecific binding. This study also illustrates how ab initio chemical methods may offer meaningful and unbiased insights for the understanding of the underlying chemical mechanisms in biological systems. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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The trans effect in square-planar platinum(II) complexes-A density functional study.

Publication Date: 2008 Apr 28 PMID: 18442081
Authors: Chval, Z. - Sip, M. - Burda, J. V.
Journal: J Comput Chem

The mechanism of substitution water exchange reactions in square planar trans-Pt[(NH(3))(2)T(H(2)O)](n+) complexes is studied (T==H(2)O, NH(3), OH(-), F(-), Cl(-), Br(-), H(2)S, CH(3)S(-), SCN(-), CN(-), PH(3), CO, CH(3) (-), H(-), C(2)H(4)). The trans effect is explained in terms of sigma-donation and pi-back-donation whose relative strengths are quantified by the changes of electron occupations of 5d platinum atomic orbitals. The sigma-donation strength is linearly correlated with the Pt--H(2)O (leaving ligand) bond length (trans influence). The kinetic trans effect strength correlates proportionally with the sigma-donation ability of the trans-ligand except the ligands with strong pi-back-donation ability that stabilizes transition state structure. The sigma-donation ability of the ligand is dependent on the sigma-donation strength of the ligand in the trans position. Therefore the trans effect caused by sigma-donation can be understood as a competition between the trans-ligands for the opportunity to donate electron density to the central Pt(II) atom. The influence of the trans effect on the reaction mechanism is also shown. For ligands with a very strong sigma-donation (e.g. CH(3) (-) and H(-)), the substitution proceeds by a dissociative interchange (I(d)) mechanism. Ligands with strong pi-back donation ability (e.g. C(2)H(4)) stabilize the pentacoordinated intermediate and the substitution proceeds by a two step associative mechanism. For ligands with weak sigma-donation and pi-back-donation abilities, the highest activation barriers have to be overcome and substitutions can be described by an associative interchange (I(a)) mechanism. The results are supported by the energy decomposition and the natural orbital analysis. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Are Ba(11)Cd(6)Sb(12) and Sr(11)Cd(6)Sb(12) Zintl phases or not? A density-functional theory study.

Publication Date: 2008 Apr 23 PMID: 18432624
Authors: Xia, S. Q. - Bobev, S.
Journal: J Comput Chem

The chemical bonding and the electronic band structures of two isoelectronic and isostructural Zintl compounds, Sr(11)Cd(6)Sb(12) and Ba(11)Cd(6)Sb(12), have been studied on the basis of the density-functional theory (DFT) using the tight-binding linear-muffin-tin-orbital (TB-LMTO-ASA) approach and the local-density approximation (LDA). These results reveal that the classic Zintl reasoning and the concept of two-center two-electron bonds cannot explain the subtleties of this complex structure type. The computations also suggest that the antimony dimers present in these structures play an important role and allow for a greater flexibility in optimization of the bonding with the surrounding d-metal atoms. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Using support vector machine to predict beta- and gamma-turns in proteins.

Publication Date: 2008 Apr 23 PMID: 18432623
Authors: Hu, X. - Li, Q.
Journal: J Comput Chem

By using the composite vector with increment of diversity, position conservation scoring function, and predictive secondary structures to express the information of sequence, a support vector machine (SVM) algorithm for predicting beta- and gamma-turns in the proteins is proposed. The 426 and 320 nonhomologous protein chains described by Guruprasad and Rajkumar (Guruprasad and Rajkumar J. Biosci 2000, 25,143) are used for training and testing the predictive model of the beta- and gamma-turns, respectively. The overall prediction accuracy and the Matthews correlation coefficient in 7-fold cross-validation are 79.8% and 0.47, respectively, for the beta-turns. The overall prediction accuracy in 5-fold cross-validation is 61.0% for the gamma-turns. These results are significantly higher than the other algorithms in the prediction of beta- and gamma-turns using the same datasets. In addition, the 547 and 823 nonhomologous protein chains described by Fuchs and Alix (Fuchs and Alix Proteins: Struct Funct Bioinform 2005, 59, 828) are used for training and testing the predictive model of the beta- and gamma-turns, and better results are obtained. This algorithm may be helpful to improve the performance of protein turns' prediction. To ensure the ability of the SVM method to correctly classify beta-turn and non-beta-turn (gamma-turn and non-gamma-turn), the receiver operating characteristic threshold independent measure curves are provided. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Extension of adaptive tree code and fast multipole methods to high angular momentum particle charge densities.

Publication Date: 2008 Apr 23 PMID: 18432622
Authors: Giese, T. J. - York, D. M.
Journal: J Comput Chem

The development and implementation of a tree code (TC) and fast multipole method (FMM) for the efficient, linear-scaling calculation of long-range electrostatic interactions of particle distributions with variable shape and multipole character are described. The target application of these methods are stochastic boundary molecular simulations with polarizable force fields and/or combined quantum mechanical/molecular mechanical potentials. Linear-scaling is accomplished through the adaptive decomposition of the system into a hierarchy of interacting particle sets. Two methods for effecting this decomposition are evaluated: fluc-splitting and box-splitting, for which the latter is demonstrated to be generally more accurate. In addition, a generalized termination criterion is developed that delivers optimal performance at fixed error tolerance that, in the case of quadrupole-represented Drude water, effects a speed-up by a factor of 2-3 relative to a multipole-independent termination criteria. The FMM is shown to be approximately 2-3 times faster than the TC, independent of the system size and multipole order of the particles. The TC and FMM are tested for a variety of static and polarizable water systems, and for the the 70S ribosome functional complex containing an assembly of transfer and messenger RNAs. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Energy density analysis for second-order Moller-Plesset perturbation theory and coupled-cluster theory with singles and doubles: Application to C(2)H(4)--CH(4) complexes.

Publication Date: 2008 Apr 23 PMID: 18432621
Authors: Imamura, Y. - Nakai, H.
Journal: J Comput Chem

Grid-based energy density analysis (EDA), in which numerical integration is performed for two-electron integrals by the pseudospectral method (Imamura et al., J. Chem. Phys. 2007, 126, 034103), is extended to correlated methods: second-order Moller-Plesset (MP2) perturbation and coupled-cluster singles and doubles (CCSD). Using EDA for MP2 and CCSD, we estimate atomic correlation energy differences and correlation energy density difference maps for C(2)H(4)--CH(4) complexes. The analyses confirm that polarization and diffuse functions essentially contribute to the descriptions of weak interaction around the nuclei and in the area between C(2)H(4) and CH(4), respectively. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Inclusion of the quadrupole moment when describing polarization. The effect of the dipole-quadrupole polarizability.

Publication Date: 2008 Apr 23 PMID: 18432620
Authors: Holt, A. - Karlstrom, G.
Journal: J Comput Chem

A method to compute distributed dipole-quadrupole polarizabilities is suggested. The method is based on numerical differentiation of distributed quadrupole moments, using finite field perturbation calculations. It is tested using two different multicenter multipole expansions, and compared with results using polarizabilities obtained via the uncoupled Hartree-Fock approximation. The accuracy of these dipole-quadrupole polarizabilities are tested for different molecules and basis sets, by comparing the induced electrostatic potential of the Hartree-Fock density with the induced electrostatic potential of the polarization models. This is done by perturbing the molecules with an external homogeneous field and with an external dipole. It is found that inclusion of the dipole-quadrupole polarizability significantly improves the accuracy of the response of the molecule to these external perturbations. This suggests that inclusion of higher-order induced moments can be of importance when improving the description of intermolecular interactions using force fields. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Unusual Sb-Sb bonding in high temperature thermoelectric materials.

Publication Date: 2008 Apr 23 PMID: 18432619
Authors: Xu, J. - Kleinke, H.
Journal: J Comput Chem

The emerging families of advanced thermoelectrics are dominated by antimonides and tellurides. Because the structures of the tellurides are mostly composed of NaCl-related motifs, they do not contain any Te-Te bonds, and all of the antimonide structures exhibit Sb-Sb bonds of various lengths. Taking all Sb-Sb distances shorter than 3.2 A into account, the Sb atom substructures are Sb(2) (4-) pairs in beta-Zn(4)Sb(3), linear Sb(3) (7-) units in Yb(14)MnSb(11), planar Sb(4) (4-) rectangles in the skutterudites, for example, LaFe(3)CoSb(12), and Sb(8) cubes interconnected via short Sb-Sb bonds to a three-dimensional network in Mo(3)Sb(5)Te(2). These interactions have a significant impact on the band gap size as well as on the effective mass around the Fermi level, for the bottom of the conduction band is in all cases predominated by antibonding Sb-Sb interactions, and-in some cases-the top of the valence band by bonding Sb-Sb interactions. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Application of the Sakurai-Sugiura projection method to core-excited-state calculation by time-dependent density functional theory.

Publication Date: 2008 Apr 23 PMID: 18432618
Authors: Tsuchimochi, T. - Kobayashi, M. - Nakata, A. - Imamura, Y. - Nakai, H.
Journal: J Comput Chem

The Sakurai-Sugiura projection (SS) method was implemented and numerically assessed for diagonalization of the Hamiltonian in time-dependent density functional theory (TDDFT). Since the SS method can be used to specify the range in which the eigenvalues are computed, it may be an efficient tool for use with eigenvalues in a particular range. In this article, the SS method is applied to core excited calculations for which the eigenvalues are located within a particular range, since the eigenvalues are unique to atomic species in molecules. The numerical assessment of formaldehyde molecule by TDDFT with core-valence Becke's three-parameter exchange (B3) plus Lee-Yang-Parr (LYP) correlation (CV-B3LYP) functional demonstrates that the SS method can be used to selectively obtain highly accurate eigenvalues and eigenvectors. Thus, the SS method is a new and powerful alternative for calculating core-excitation energies without high computation costs. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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The Poisson-Boltzmann model for tRNA: Assessment of the calculation set-up and ionic concentration cutoff.

Publication Date: 2008 Apr 23 PMID: 18432617
Authors: Gruziel, M. - Grochowski, P. - Trylska, J.
Journal: J Comput Chem

Using tRNA molecule as an example, we evaluate the applicability of the Poisson-Boltzmann model to highly charged systems such as nucleic acids. Particularly, we describe the effect of explicit crystallographic divalent ions and water molecules, ionic strength of the solvent, and the linear approximation to the Poisson-Boltzmann equation on the electrostatic potential and electrostatic free energy. We calculate and compare typical similarity indices and measures, such as Hodgkin index and root mean square deviation. Finally, we introduce a modification to the nonlinear Poisson-Boltzmann equation, which accounts in a simple way for the finite size of mobile ions, by applying a cutoff in the concentration formula for ionic distribution at regions of high electrostatic potentials. We test the influence of this ionic concentration cutoff on the electrostatic properties of tRNA. (c) 2008 Wiley Periodicals, Inc. J Comput Chem, 2008.

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Effects of electron attachment on C(5')--O(5') and C(1')--N(1) bond cleavages of pyrimidine nucleotides: A theoretical study.

Publication Date: 2008 Apr 23 PMID: 18432616
Authors: Xie, H. - Wu, R. - Xia, F. - Cao, Z.
Journal: J Comput Chem

Sugar-base C(1')--N(1) and phosphate-sugar C(5')--O(5') bond breakings of 2'-deoxycytidine-5'-monophosphates (dCMP) and 2'-deoxythymidine-5'- monophosphates (dTMP) and their radical anions have been explored theoretically at the B3LYP/DZP++ level of theory. Calculations show that the low-energy electrons attachment to the pyrimidine nucleotides results in remarkable structural and chemical bonding changes. Predicted Gibbs free energies of reaction DeltaG for the C(5')--O(5') bond dissociation process of the radical anions are -14.6 and -11.5 kcal mol(-1), respectively, and such dissociation processes may be intrinsically spontaneous in the gas phase. Furthermore, the C(5')--O(5') bond cleavage processes of the anionic dCMP and dTMP were predicted to have activation energies of 6.9 and 8.0 kcal mol(-1) in the gas phase, respectively, much lower than the barriers for the C(1')--N(1) bond breaking process, showing that the C--O bond dissociation in DNA single strand breaks is a dominant process as observed experimentally. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Exploring the conformational space of Vpu from HIV-1: A versatile adaptable protein.

Publication Date: 2008 Apr 23 PMID: 18432615
Authors: Kruger, J. - Fischer, W. B.
Journal: J Comput Chem

The dynamic behavior of monomeric Vpu(1-32) from HIV-1 in different lipid environments has been studied. The peptide shows highly flexible behavior during the simulations and easily adapts to changing lipid environments as it experiences when travelling through the Golgi apparatus. Protein-lipid interactions do not show any significant correlation towards lipid type or thickness based on multiple 10 ns simulations. The averaged structure of a series of 16 independent simulations suggest kink around Ser-24, which compensates the polarity of its side chain by forming hydrogen bonds with the carbonyl backbone of adjacent amino acids towards the N-terminus. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Electron localizability for hexagonal element structures.

Publication Date: 2008 Apr 23 PMID: 18432614
Authors: Baranov, A. I. - Kohout, M.
Journal: J Comput Chem

For 21 elements crystallizing in hexagonal structure density functional calculations were performed. The topology of the electron localizability indicator (ELI) allows classifying the elements as appertaining to one of six patterns. The bifurcation diagrams as well as the electron populations in ELI basins for each pattern are discussed. (c) 2008 Wiley Periodicals, Inc. J Comput Chem 2008.

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Associative versus dissociative binding of CO to 4d transition metal trimers: A density functional study.

Publication Date: 2008 Jul 15 PMID: 18393258
Authors: Addicoat, M. A. - Buntine, M. A. - Yates, B. - Metha, G. F.
Journal: J Comput Chem

Density functional calculations were performed to determine equilibrium geometrical structures, transition states and relative energies for M(3) clusters (M = Nb, Mo, Tc, Ru, Rh, Pd, Ag) reacting with CO, leading to proposed reaction pathways. For the Nb(3), Mo(3), and Tc(3) clusters, the lowest energy structure correlates to dissociated CO, with the C and O atoms bound on opposite sides of the metal triangle. For all other trimers, the lowest energy structures maintain the CO moiety. In the case of Pd(3) and Ag(3) the dissociated geometries lie higher in energy than the sum of the separated reactants. In most cases, several multiplicities were found to be similar in energy and for Mo(3)CO and Pd(3)CO singlet-triplet minimum energy crossing points were identified. In the case of Rh(3)CO, minimum energy crossing points for the doublet, quartet, and sextet reaction pathways were determined and compared. The electron densities of pertinent M(3)CO species were investigated using Natural Bond Order calculations. It was found that the effect of the metal trimer on the energy of the pure p-type pi* antibonding orbital of carbon monoxide directly correlates with the occurrence of CO dissociation.

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Advancing beyond charge analysis using the electronic localization function: Chemically intuitive distribution of electrostatic moments.

Publication Date: 2008 Jul 15 PMID: 18293309
Authors: Pilme, J. - Piquemal, J. P.
Journal: J Comput Chem

We propose here an evaluation of chemically intuitive distributed electrostatic moments using the topological analysis of the electron localization function (ELF). As this partition of the total charge density provides an accurate representation of the molecular dipole, the distributed electrostatic moments based on the ELF partition (DEMEP) allows computing of local moments located at non atomic centers such as lone pairs, sigma bonds and pi systems. As the local dipole contribution can be decomposed in polarization and charge transfer components, our results indicate that local dipolar polarization of the lone pairs and chemical reactivity are closely related whereas the charge transfer contribution is the key factor driving the local bond dipole. Results on relevant molecules show that local dipole contributions can be used to rationalize inductive polarization effects in alcohols derivatives and typical hydrogen bond interactions. Moreover, bond quadrupole polarization moments being related to a pi character enable to discuss bond multiplicities, and to sort families of molecules according to their bond order. That way, the nature of the C-O bond has been revisited for several typical systems by means of the DEMEP analysis which appears also helpful to discuss aromaticity. Special attention has been given to the carbon monoxide molecule, to the CuCO complex and to a weak intramolecular N|-CO interaction involved in several biological systems. In this latter case, it is confirmed that the bond formation is mainly linked to the CO bond polarization. Transferability tests show that the approach is suitable for the design of advanced force fields.

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RNACluster: An integrated tool for RNA secondary structure comparison and clustering.

Publication Date: 2008 Jul 15 PMID: 18271070
Authors: Liu, Q. - Olman, V. - Liu, H. - Ye, X. - Qiu, S. - Xu, Y.
Journal: J Comput Chem

RNA structure comparison is a fundamental problem in structural biology, structural chemistry, and bioinformatics. It can be used for analysis of RNA energy landscapes, conformational switches, and facilitating RNA structure prediction. The purpose of our integrated tool RNACluster is twofold: to provide a platform for computing and comparison of different distances between RNA secondary structures, and to perform cluster identification to derive useful information of RNA structure ensembles, using a minimum spanning tree (MST) based clustering algorithm. RNACluster employs a cluster identification approach based on a MST representation of the RNA ensemble data and currently supports six distance measures between RNA secondary structures. RNACluster provides a user-friendly graphical interface to allow a user to compare different structural distances, analyze the structure ensembles, and visualize predicted structural clusters.

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Efficient model chemistries for peptides. I. General framework and a study of the heterolevel approximation in RHF and MP2 with Pople split-valence basis sets.

Publication Date: 2008 Jul 15 PMID: 18270966
Authors: Echenique, P. - Alonso, J. L.
Journal: J Comput Chem

We present an exhaustive study of more than 250 ab initio potential energy surfaces (PESs) of the model dipeptide HCO-L-Ala-NH(2). The model chemistries (MCs) investigated are constructed as homo- and heterolevels involving possibly different RHF and MP2 calculations for the geometry and the energy. The basis sets used belong to a sample of 39 representants from Pople's split-valence families, ranging from the small 3-21G to the large 6-311++G(2df,2pd). The reference PES to which the rest are compared is the MP2/6-311++G(2df,2pd) homolevel, which, as far as we are aware, is the most accurate PES in the literature. All data sets have been analyzed according to a general framework, which can be extended to other complex problems and which captures the nearness concept in the space of MCs. The great number of MCs evaluated has allowed us to significantly explore this space and show that the correlation between accuracy and computational cost of the methods is imperfect, thus justifying a systematic search for the combination of features in a MC that is optimal to deal with peptides. Regarding the particular MCs studied, the most important conclusion is that the potentially very cost-saving heterolevel approximation is a very efficient one to describe the whole PES of HCO-L-Ala-NH(2). Finally, we show that, although RHF may be used to calculate the geometry if a MP2 single-point energy calculation follows, pure RHF//RHF homolevels are not recommendable for this problem.

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Retrieval of spectral and dynamic properties from two-dimensional infrared pump-probe experiments.

Publication Date: 2008 Jul 15 PMID: 18270965
Authors: Chelli, R. - Volkov, V. V. - Righini, R.
Journal: J Comput Chem

We have developed a fitting algorithm able to extract spectral and dynamic properties of a three level oscillator from a two-dimensional infrared spectrum (2D-IR) detected in time resolved nonlinear experiments. Such properties go from the frequencies of the ground-to-first and first-to-second vibrational transitions (and hence anharmonicity) to the frequency-fluctuation correlation function. This last is represented through a general expression that allows one to approach the various strategies of modeling proposed in the literature. The model is based on the Kubo picture of stochastic fluctuations of the transition frequency as a result of perturbations by a fluctuating surrounding. To account for the line-shape broadening due to pump pulse spectral width in double-resonance measurements, we supply the fitting algorithm with the option to perform the convolution of the spectral signal with a Lorentzian function in the pump-frequency dimension. The algorithm is tested here on 2D-IR pump-probe spectra of a Gly-Ala dipeptide recorded at various pump-probe delay times. Speedup benchmarks have been performed on a small Beowulf cluster. The program is written in FORTRAN language for both serial and parallel architectures and is available free of charge to the interested reader.

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Coarse-grained force field for the nucleosome from self-consistent multiscaling.

Publication Date: 2008 Jul 15 PMID: 18270964
Authors: Voltz, K. - Trylska, J. - Tozzini, V. - Kurkal-Siebert, V. - Langowski, J. - Smith, J.
Journal: J Comput Chem

A coarse-grained simulation model for the nucleosome is developed, using a methodology modified from previous work on the ribosome. Protein residues and DNA nucleotides are represented as beads, interacting through harmonic (for neighboring) or Morse (for nonbonded) potentials. Force-field parameters were estimated by Boltzmann inversion of the corresponding radial distribution functions obtained from a 5-ns all-atom molecular dynamics (MD) simulation, and were refined to produce agreement with the all-atom MD simulation. This self-consistent multiscale approach yields a coarse-grained model that is capable of reproducing equilibrium structural properties calculated from a 50-ns all-atom MD simulation. This coarse-grained model speeds up nucleosome simulations by a factor of 10(3) and is expected to be useful in examining biologically relevant dynamical nucleosome phenomena on the microsecond timescale and beyond.

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DFT study of the cryptand and benzocryptand and their complexes with alkali metal cations: Li+, Na+, K+.

Publication Date: 2008 Jul 15 PMID: 18270963
Authors: Wang, X. - Wang, H. - Tan, Y.
Journal: J Comput Chem

In the present work, a theoretical study of the cryptand 4, 7, 13, 16, 21, 24-hexaoxa-1, 10- diazabicyclo [8,8,8] hexacosan (the named [222]) and the cryptand 5, 6-benzo-4, 7, 13, 16, 21, 24-hexaoxa-1, 10-diazabicyclo [8, 8, 8] hexacosan (the nemed [222B]) had been done using density functional theory (DFT) with B3LYP/6-31G* method in order to obtain the electronic and geometrical structure of the cryptands and their complexes with alkali metal ions: Li(+), Na(+), and K(+). The nucleophilicity of cryptands had been investigated by the Fukui function. For complexes, the match between cation and cavity size, the status of interaction between alkali metal ions and donor atoms in the cryptands and the rigidity of the cryptands had been analyzed through the other calculated parameters. In addition, the enthalpies of complexation reaction and cation exchange reaction had been studied by the calculated thermodynamic data. The calculated results are in a good agreement with the experimental data for the complexes.

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The calculation of static polarizabilities of 1-3D periodic compounds. the implementation in the crystal code.

Publication Date: 2008 Jul 15 PMID: 18270962
Authors: Ferrero, M. - Rerat, M. - Orlando, R. - Dovesi, R.
Journal: J Comput Chem

The Coupled Perturbed Hartree-Fock (CPHF) scheme has been implemented in the CRYSTAL06 program, that uses a gaussian type basis set, for systems periodic in 1D (polymers), 2D (slabs), 3D (crystals) and, as a limiting case, 0D (molecules), which enables comparison with molecular codes. CPHF is applied to the calculation of the polarizability alpha of LiF in different aggregation states: finite and infinite chains, slabs, and cubic crystal. Correctness of the computational scheme for the various dimensionalities and its numerical efficiency are confirmed by the correct trend of alpha: alpha for a finite linear chain containing N LiF units with large N tends to the value for the infinite chain, N parallel chains give the slab value when N is sufficiently large, and N superimposed slabs tend to the bulk value. CPHF results compare well with those obtained with a saw-tooth potential approach, previously implemented in CRYSTAL. High numerical accuracy can easily be achieved at relatively low cost, with the same kind of dependence on the computational parameters as for the SCF cycle. Overall, the cost of one component of the dielectric tensor is roughly the same as for the SCF cycle, and it is dominated by the calculation of two-electron four-center integrals.

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The effect of electron correlation on the conformational space of melatonin.

Publication Date: 2008 Jul 15 PMID: 18270961
Authors: Csontos, J. - Kalman, P. - Tasi, G. - Kalman, M. - Murphy, R. F. - Lovas, S.
Journal: J Comput Chem

The pineal gland hormone melatonin regulates several physiological processes including circadian rhythm and also alleviates oxidative stress-induced degenerative diseases. In spite of its important biological roles, no high level ab initio conformational study has been conducted to reveal its structural features. In this work, the conformational flexibility of melatonin was investigated using correlated ab initio calculations. Conformers, obtained previously at the Hartree-Fock level (HF/6-31G*), were fully optimized using second order Moller-Plesset perturbation theory applying the frozen core approximation (MP2(FC)/6-31G*). Furthermore, single-point MP4(SDQ,FC)/6-31G*//MP2(FC)/6-31G* computations were performed to investigate the effect of higher order perturbation terms. The HF and MP2 conformational spaces are considerably different: the initial 128 structures converged into 102 different local minima as confirmed by frequency calculations; 28 new minima appeared and 26 previous HF local minima disappeared; no "all-trans" C3 side chain conformations are seen at the MP2(FC) level. The MP2 global minimum conformation is stabilized by an aromatic-side chain interaction.

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Collective motions of rigid fragments in protein structures from smoothed electron density distributions.

Publication Date: 2008 Jul 15 PMID: 18270960
Authors: Leherte, L. - Vercauteren, D. P.
Journal: J Comput Chem

In this work, the Gaussian Network Model (GNM) and Anisotropic Network Model (ANM) approaches are applied to describe the dynamics of protein structure graphs built from calculated promolecular electron density (ED) distribution functions. A first set of analyses is carried out on results obtained from ED maxima calculated at various smoothing levels. A second set is achieved for ED networks whose edges are weighted by ED overlap integral values. Results are compared with those obtained through the classical GNM and ANM approaches applied to networks of C(alpha) atoms. It is shown how the network model and the consideration of crystal packing as well as of the side chains may lead to various improvements dependent upon the structure under study. The selected protein structures are Crambin and Pancreatic Trypsin Inhibitor because of their small size and numerous dynamical data obtained by other authors.

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Blue shifts of the C-H stretching vibrations in hydrogen-bonded and protonated trimethylamine. Effect of hyperconjugation on bond properties.

Publication Date: 2008 Jul 15 PMID: 18270959
Authors: Chandra, A. K. - Parveen, S. - Das, S. - Zeegers-Huyskens, T.
Journal: J Comput Chem

The optimized geometry of isolated trimethylamine (TMA), its hydrogen bond complexes with phenol derivatives and protonated TMA is calculated at the B3LYP/6-31++G(d,p) level. A natural bond orbital (NBO) analysis on these systems is carried out at the same level of theory. In isolated TMA, one of the C-H bond in each of the three CH(3) groups is more elongated than the two other ones. As revealed by the NBO data, this results from a hyperconjugative interaction from the N lone pair to the sigma*(C-H) orbitals of the C-H bonds being in a transoid position with respect to the N lone pair. The formation of an intermolecular OH...N hydrogen bond with phenols results in a decrease of the lone pair effect. A linear correlation is found between the decrease in occupation of the sigma*(C-H) orbitals and the decrease in the hyperconjugative interaction energy in the complexes and isolated TMA. Complex formation with phenols results in a blue shift of 55-74 cm(-1) of the C-H stretching vibrations involved in the lone pair effect. Smaller blue shifts between 14 and 23 cm(-1) are predicted for the other C-H bonds. In these complexes, a linear correlation is found between the frequency shifts and the elongation of the C-H bonds. Protonation of TMA results in a nearly equalization of all the C-H distances and a blue shift of 180 cm(-1) of the C-H bonds involved in hyperconjugation with the N lone pair.

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A reactive bond orbital investigation of the Diels-Alder reaction between 1,3-butadiene and ethylene: Energy decomposition, state correlation diagram, and electron density analyses.

Publication Date: 2008 Jul 15 PMID: 18213608
Authors: Hirao, H.
Journal: J Comput Chem

The reactive bond orbital (RBO) method (Hirao, Chem Phys Lett 2007, 443, 141) is extended and applied to the Diels-Alder reaction between 1,3-butadiene and ethylene, with the aim of understanding the nature of their interaction. The roles of distortion, electrostatic, exchange, polarization, and charge transfer (CT) interaction energies at the transition state of the reaction are evaluated by means of RBO energy decomposition analysis. The effects of the hypothetical interactions on electron density redistribution are also identified by analysis based on the RBO method. CT is shown to play essential roles in the new bond formation between the reacting molecules and their internal bond order alterations. However, each of the CT interactions from butadiene to ethylene and from ethylene to butadiene does not necessarily contribute to the bond-order alteration process effectively. A state correlation diagram approach based on the RBO method is also proposed, and its usefulness in understanding the origin of the barrier in the Diels-Alder reaction is demonstrated.

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Structure and bonding in binuclear metal carbonyls from the analysis of domain averaged Fermi holes. I. Fe2(CO)9 and Co2(CO)8.

Publication Date: 2008 Jul 15 PMID: 18196504
Authors: Ponec, R. - Lendvay, G. - Chaves, J.
Journal: J Comput Chem

The nature of the bonding in the above carbonyls was studied using the analysis of domain averaged Fermi holes (DAFH). The results straightforwardly confirm the conclusions of earlier theoretical studies in which the existence of direct metal-metal bond, anticipated for the above carbonyls on the basis of 18-electron rule, was questioned. In addition to indicating the lack of direct metal-metal bond, the DAFH analysis also allowed to characterize the nature of the electron pairs involved in the bonding of the bridging ligands. The analysis has shown that because the number of available electron pairs is not sufficient for the formation of ordinary localized 2c-2e bonds between terminal M(CO)(3) fragments and the bridging ligands, the bonding in both carbonyls exhibits typical features of electron deficiency and one bonding electron pair is effectively involved in multicenter 3c-2e bonding. Because of the symmetry of the complexes the bridging ligands are not distinguishable and all M-C-M bridges have a partial 3c-2e nature via resonance of the localized structures.

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How stable is a collagen triple helix? An ab initio study on various collagen and beta-sheet forming sequences.

Publication Date: 2008 Jul 15 PMID: 18196503
Authors: Palfi, V. K. - Perczel, A.
Journal: J Comput Chem

Collagen forms the well characterized triple helical secondary structure, stabilized by interchain H-bonds. Here we have investigated the stability of fully optimized collagen triple helices and beta-pleated sheets by using first principles (ab initio and DFT) calculations so as to determine the secondary structure preference depending on the amino acid composition. Models composed of a total of 18 amino acid residues were studied at six different amino acid compositions: (i) L-alanine only, (ii) glycine only, (iii) L-alanines and glycine, (iv) L-alanines and D-alanine, (v) L-prolines with glycine, (vi) L-proline, L-hydroxyproline, and glycine. The last two, v and vi, were designed to mimic the core part of collagen. Furthermore, ii, iii, and iv model the binding and/or recognition sites of collagen. Finally, i models the G-->A replacement, rare in collagen. All calculated structures show great resemblance to those determined by X-ray crystallography. Calculated triple helix formation affinities correlate well with experimentally determined stabilities derived from melting point (T(m)) data of different collagen models. The stabilization energy of a collagen triple helical structure over that of a beta-pleated sheet is 2.1 kcal mol(-1) per triplet for the [(-Pro-Hyp-Gly-)(2)](3) collagen peptide. This changes to 4.8 kcal mol(-1) per triplet of destabilization energy for the [(-Ala-Ala-Gly-)(2)](3) sequence, known to be disfavored in collagen. The present study proves that by using first principles methods for calculating stabilities of supramolecular complexes, such as collagen and beta-pleated sheets, one can obtain stability data in full agreement with experimental observations, which envisage the applicability of QM in molecular design.

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Fast procedure for reconstruction of full-atom protein models from reduced representations.

Publication Date: 2008 Jul 15 PMID: 18196502
Authors: Rotkiewicz, P. - Skolnick, J.
Journal: J Comput Chem

We introduce PULCHRA, a fast and robust method for the reconstruction of full-atom protein models starting from a reduced protein representation. The algorithm is particularly suitable as an intermediate step between coarse-grained model-based structure prediction and applications requiring an all-atom structure, such as molecular dynamics, protein-ligand docking, structure-based function prediction, or assessment of quality of the predicted structure. The accuracy of the method was tested on a set of high-resolution crystallographic structures as well as on a set of low-resolution protein decoys generated by a protein structure prediction algorithm TASSER. The method is implemented as a standalone program that is available for download from http://cssb.biology.gatech.edu/skolnick/files/PULCHRA.

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Ab initio determination of the flexibility of 2'-aminoribonucleosides and 2'-aminoarabinonucleosides inserted in duplexes.

Publication Date: 2008 Jul 15 PMID: 18181138
Authors: Barbe, S. - Le Bret, M.
Journal: J Comput Chem

The sugar puckering of adenosine and uridine nucleosides with an amino group at 2' in the ribo or arabino orientations are determined using high-level quantum mechanical calculations Only the conformations that have dihedrals compatible with their insertion into a duplex are retained. The amino group has always been found to be pyramidal and its orientation governs the conformation of the sugar. The energetically most favorable conformation of the 2'-aminoribonucleosides has the south puckering but must be discarded. For another orientation of the 2'-amino group, the conformation is energetically less favorable but has the north puckering. Calculations performed in the presence of a water molecule give similar results but with a smaller energy gap. The model then explains why the insertion of a 2'-aminoribonucleotide destabilizes double-stranded RNAs and also double-stranded DNAs. In the arabino orientation, an NH(2) substituent at 2' favors north puckering. In contrast to 2'-aminoribonucleosides, deoxynucleosides inserted into a duplex remain in the most energetically favorable conformation compatible with the canonical values of the torsion angles. The whole relaxed potential map, in the amplitude/pseudorotation space, shows that for natural deoxyadenosine there is only one valley in the east running from south to north puckering.

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Soft energy function and generic evolutionary method for discriminating native from nonnative protein conformations.

Publication Date: 2008 Jul 15 PMID: 18181137
Authors: Chiu, Y. Y. - Hwang, J. K. - Yang, J. M.
Journal: J Comput Chem

We have developed a soft energy function, termed GEMSCORE, for the protein structure prediction, which is one of emergent issues in the computational biology. The GEMSORE consists of the van der Waals, the hydrogen-bonding potential and the solvent potential with 12 parameters which are optimized by using a generic evolutionary method. The GEMSCORE is able to successfully identify 86 native proteins among 96 target proteins on six decoy sets from more 70,000 near-native structures. For these six benchmark datasets, the predictive performance of the GEMSCORE, based on native structure ranking and Z-scores, was superior to eight other energy functions. Our method is based solely on a simple and linear function and thus is considerably faster than other methods that rely on the additional complex calculations. In addition, the GEMSCORE recognized 17 and 2 native structures as the first and the second rank, respectively, among 21 targets in CASP6 (Critical Assessment of Techniques for Protein Structure Prediction). These results suggest that the GEMSCORE is fast and performs well to discriminate between native and nonnative structures from thousands of protein structure candidates. We believe that GEMSCORE is robust and should be a useful energy function for the protein structure prediction.

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Atoms-in-molecules analysis for planewave DFT calculations--a numerical approach on a successively interpolated charge density grid.

Publication Date: 2008 Jun PMID: 18172841
Authors: Yim, W. L. - Kluner, T.
Journal: J Comput Chem

We used a successive charge interpolation scheme and Ridders method for differentiation, to acquire accurate charge densities and their higher derivatives in electronic structure calculations. This enables us to search bond critical points using arbitrary charge density grids. We applied the planewave-DFT code, VASP, to generate the charge density of selected benchmark molecules. The properties of bond critical points are in good agreement with those obtained by complementary implementations. We validated our GRID implementation by performing electronic structure calculations using the Gaussian 03 program package and various tools for analysis of the charge density provided by the AIMPAC package. In particular, we carefully investigate the influence of effective core potentials on the location of bond critical points, especially for a short chemical bond, which is crucial in the present pseudopotential-based planewave DFT calculations. We expect our generic implementation will not only be useful for the analysis of chemical bonding in molecules, but will particularly provide a microscopic understanding of extended systems including periodic boundary conditions.

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Use of statistical measures for analyzing RNA secondary structures.

Publication Date: 2008 Jun PMID: 18172840
Authors: Dai, Q. - Wang, T. M.
Journal: J Comput Chem

With more and more RNA secondary structures accumulated, the need for comparing different RNA secondary structures often arises in function prediction and evolutionary analysis. Numerous efficient algorithms were developed for comparing different RNA secondary structures, but challenges remain. In this article, a new statistical measure extending the notion of relative entropy based on the proposed stochastic model is evaluated for RNA secondary structures. The results obtained from several experiments on real datasets have shown the effectiveness of the proposed approach. Moreover, the time complexity of our method is favorable by comparing with that of the existing methods which solve the similar problem.

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Kirchhoff atomic charges fitted to multipole moments: implementation for a virtual screening system.

Publication Date: 2008 Jun PMID: 18172839
Authors: Yakovenko, O. - Oliferenko, A. A. - Bdzhola, V. G. - Palyulin, V. A. - Zefirov, N. S.
Journal: J Comput Chem

The Kirchhoff charge model is a viable method of generating inexpensive and electrostatically reasonable atomic charges for molecular mechanical force fields. The charging method uses a computationally fast algorithm based on the principle of electronegativity relaxation. Parameters of the method, orbital electronegativities and hardnesses, are fitted to reproduce reference, ab initio calculated dipole and quadrupole moments of a representative training set of neutral and charged organic molecules covering most medicinal chemistry relevant bonding situations. Transferability and accuracy of the derived parameters are confirmed on an external test set. Comparisons to other charge models are made. Implementation of the new Kirchhoff charges into a virtual screening engine is elucidated.

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Assessment of programs for ligand binding affinity prediction.

Publication Date: 2008 Jun PMID: 18172838
Authors: Kim, R. - Skolnick, J.
Journal: J Comput Chem

The prediction of the binding free energy between a ligand and a protein is an important component in the virtual screening and lead optimization of ligands for drug discovery. To determine the quality of current binding free energy estimation programs, we examined FlexX, X-Score, AutoDock, and BLEEP for their performance in binding free energy prediction in various situations including cocrystallized complex structures, cross docking of ligands to their non-cocrystallized receptors, docking of thermally unfolded receptor decoys to their ligands, and complex structures with "randomized" ligand decoys. In no case was there a satisfactory correlation between the experimental and estimated binding free energies over all the datasets tested. Meanwhile, a strong correlation between ligand molecular weight-binding affinity correlation and experimental predicted binding affinity correlation was found. Sometimes the programs also correctly ranked ligands' binding affinities even though native interactions between the ligands and their receptors were essentially lost because of receptor deformation or ligand randomization, and the programs could not decisively discriminate randomized ligand decoys from their native ligands; this suggested that the tested programs miss important components for the accurate capture of specific ligand binding interactions.

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Calculation of weakly polar interaction energies in polypeptides using density functional and local Moller-Plesset perturbation theory.

Publication Date: 2008 Jun PMID: 18172837
Authors: Csontos, J. - Palermo, N. Y. - Murphy, R. F. - Lovas, S.
Journal: J Comput Chem

The interaction energies of ubiquitous weakly polar interactions in proteins are comparable with those of hydrogen bonds, consequently, they stabilize local, secondary, and tertiary structures. However, the most widely-used density functionals fail to describe the weakly polar interactions. Thus, it is important to find and test functionals which adequately describe and quantify the energetics of such interactions. For this purpose, interaction energies in the hydrophobic core of rubredoxin (PDB id: 1rb9) and in the S22 subset of the JSCH-2005 benchmark database were computed with the BHandHLYP and PWPW91 functionals and with the pseudospectral implementation of the local MP2 (PS-LMP2) method. The cc-pVDZ, cc-pVTZ(-f), cc-pVTZ, cc-pVQZ(-g), aug-cc-pVDZ, aug-cc-VTZ(-f), and aug-cc-pVTZ basis sets were used for the calculations. In the S22 subset the PS-LMP2 results were extrapolated to the complete basis set limit. Furthermore, the a posteriori counterpoise method of Boys and Bernardi was used to correct the basis set superposition errors in the calculation of interaction energies. Calculations using the BHandHLYP functional, both for the various weakly polar interactions in rubredoxin and for the dispersion interactions in the S22 subset, were in good agreement with those using the coupled cluster (CCSD(T)) and the resolution of identity MP2 (RIMP2) methods and clearly outperformed both the PWPW91 functional and the PS-LMP2 method. The results for the S22 hydrogen bonded subset, obtained with PWPW91 calculations, were closest to those of the reference high level calculations. For the "mixed" (hydrogen bonded and dispersive) interactions in the S22 subset, results obtained with the BHandHLYP and PS-LMP2 calculations agreed well with the reference calculations.

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Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine: water-assisted mechanism and cluster-continuum model.

Publication Date: 2008 Jun PMID: 18161688
Authors: Wu, Y. - Jin, L. - Xue, Y. - Xie, D. Q. - Kim, C. K. - Guo, Y. - Yan, G. S.
Journal: J Comput Chem

The hydrolysis reaction of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine (DMPFA), a model compound of the antivirus drug amidine-3TC (3TC = 2', 3'-dideoxy-3'-thiacytidine), is investigated by the hybrid density functional theory B3LYP/6-31+G (d,p) method. The hydrolysis reaction of the title compound is predicted to undergo via two pathways, each of which is a stepwise process. Path A is the addition of H2O to the C=N double bond in the amidine group to form a tetrahedral structure in its first step, and then the transfer of the H atom of hydroxyl leads to the corresponding products via four possible channels. Path B simultaneously involves the nucleophilic attack of H2O to the C atom of the C=N bond and the proton transfer to the N atom of amino group leading to the cleavage of the C-N single bond in the amidine group. The results indicate that path A is more favorable than path B in the gas phase. Moreover, to simulate the title reaction in aqueous solution, water-assisted mechanism and the cluster-continuum model, based on the SCRF/CPCM model, are taken into account in our work. The results indicate that it is rational for two water molecules served as a bridge to assist in the first step of path A and that cytosine rather than the cytosine-substituted formamide should be released from the tetrahedral intermediate via s six-membered cycle transition state (channel 2). Our calculations exhibit that the process toward the tetrahedral intermediate is the rate-determining step both in the gas phase and in aqueous solution.

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