Journal of Computational Chemistry

Corcho, Francesc J.; Canto, Josep; Perez, Juan J.

doi: 10.1002/jcc.20114pmid: 15457496

The present study describes an extensive conformational search of substance P using two different computational methods. On the one hand, the peptide was studied using the iterative simulated annealing, and on the other, molecular dynamics simulations at 300 and 400 K. With the former method, the peptide was studied in vacuo with a dielectric constant of 80, whereas using the latter study the peptide was studied in a box of TIP3P water molecules. Analysis of the results obtained using both methodologies was carried out using an in‐house methodology using a cluster analysis method based on information theory. Comparison of the two sampling methodologies and the different environment used in the calculations is also analyzed. Finally, the conformational motifs that are characteristic of substance P in a hydrophilic environment are presented and compared with the experimental results available in the literature. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1937–1952, 2004

Hayes, Joseph M.; Greer, James C.; Morton–Blake, David A.

doi: 10.1002/jcc.20116pmid: 15470758

The use of Buckingham (exp‐6) van der Waals potentials in molecular dynamics (MD) simulations can quite successfully reproduce experimental thermodynamic data at low densities. However, they are less successful in producing a description of the repulsive regions of the potential energy surface (PES) that is in accord with the results of high‐level ab initio computations. We show that Morse potentials can be parameterized to give excellent fits to both the attractive and repulsive regions of the PES. The best set of alkane van der Waals Morse function parameters reported to date for the description of nonbond repulsive interactions is presented, as determined by comparison with both ab initio and experimental results. C…C, H…H and C…H atom‐pair potentials employing parameter sets based on the use of the geometric mean in the fitting procedure are found to be portable from methane to n‐butane. Fitting to a combination of methane dimer interaction energies and forces from ab initio calculations yields parameter sets whose performance is superior to those determined from the interaction energies alone. Used in MD simulations, our newly developed parameter sets predict thermodynamic functions that show better agreement with experiment than those based on parameter sets in common use. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1953–1966, 2004

Lee, Michael S.; Salsbury, Freddie R.; Olson, Mark A.

doi: 10.1002/jcc.20119pmid: 15470756

We present a new hybrid explicit/implicit solvent method for dynamics simulations of macromolecular systems. The method models explicitly the hydration of the solute by either a layer or sphere of water molecules, and the generalized Born (GB) theory is used to treat the bulk continuum solvent outside the explicit simulation volume. To reduce the computational cost, we implemented a multigrid method for evaluating the pairwise electrostatic and GB terms. It is shown that for typical ion and protein simulations our method achieves similar equilibrium and dynamical observables as the conventional particle mesh Ewald (PME) method. Simulation timings are reported, which indicate that the hybrid method is much faster than PME, primarily due to a significant reduction in the number of explicit water molecules required to model hydration effects. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1967–1978, 2004

Exner, Otto; Böhm, Stanislav

doi: 10.1002/jcc.20124pmid: 15470757

Energies of hydrocarbon monoderivatives CH3X, C2H5X, n‐C4H9X, and n‐C5H11X with 16 different substituents X were calculated at the levels B3LYP/6‐311+G(d,p) and B3LYP/AUG‐cc‐pVTZ//B3LYP/6‐311+G(d,p). The results were used to test the validity of the additive rule that has served commonly for estimating the enthalpies of formation ΔfH(T). The exact additivity corresponds to zero reaction energy ΔE of the isodesmic reaction, in which the substituent X is transferred from one alkyl group R to another. Additivity is approximately fulfilled for butyl and pentyl derivatives with the differences less than 0.3 kJ mol−1 (except charged groups X). Methyl derivatives deviated from the additive rule up to 22 kJ mol−1 for dipolar groups X and 45 kJ mol−1 for charged group, in agreement with the available experiments and with the anticipation of all suggested empirical schemes. In addition, smaller deviations of ethyl derivatives (3 or 20 kJ mol−1, respectively) were observed here for the first time. There is no correlation between the deviations of methyl and ethyl derivatives; they are also not related to steric effects, and only partly to polarization. Deviations of methyl derivatives are proportional to the electronegativity of the first atom of the substituent; even when the definition of electronegativity is somewhat questionable, one can say in any case that it is controlled by the first atom. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1979–1986, 2004

Fernández Rico, J.; López, R.; Ema, I.; Ramírez, G.

doi: 10.1002/jcc.20131pmid: 15473010

The performances of the algorithms employed in a previously reported program for the calculation of integrals with Slater‐type orbitals are examined. The integrals are classified in types and the efficiency (in terms of the ratio accuracy/cost) of the algorithm selected for each type is analyzed. These algorithms yield all the one‐ and two‐center integrals (both one‐ and two‐electron) with an accuracy of at least 12 decimal places and an average computational time of very few microseconds per integral. The algorithms for three‐ and four‐center electron repulsion integrals, based on the discrete Gauss transform, have a computational cost that depends on the local symmetry of the molecule and the accuracy of the integrals, standard efficiency being in the range of eight decimal places in hundreds of microseconds. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1987–1994, 2004

Tatsumi, Rie; Fukunishi, Yoshifumi; Nakamura, Haruki

doi: 10.1002/jcc.20133pmid: 15473011

We have developed a new docking method to consider receptor flexibility, a hybrid method of molecular dynamics and harmonic dynamics. The global motions of the whole receptor were approximately introduced into those of the receptor in the docking simulation as harmonic dynamics. On the other hand, the local flexibility of the side chains was also considered by conventional molecular dynamics. We confirmed that this new method can reproduce the fluctuations of the whole receptor by making a comparison of the directions and amplitudes of the global fluctuations. Then this method was applied to the docking of HIV‐1 protease and its ligand. As a result, we observed a docking process where the ligand enters into the binding pocket well, which implies that this method is effective enough to reproduce a molecular complex formation. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1995–2005, 2004

Vadali, Ramkumar V.; Shi, Yan; Kumar, Sameer; Kale, Laxmikant V.; Tuckerman, Mark E.; Martyna, Glenn J.

doi: 10.1002/jcc.20113pmid: 15473008

Many systems of great importance in material science, chemistry, solid‐state physics, and biophysics require forces generated from an electronic structure calculation, as opposed to an empirically derived force law to describe their properties adequately. The use of such forces as input to Newton's equations of motion forms the basis of the ab initio molecular dynamics method, which is able to treat the dynamics of chemical bond‐breaking and ‐forming events. However, a very large number of electronic structure calculations must be performed to compute an ab initio molecular dynamics trajectory, making the efficiency as well as the accuracy of the electronic structure representation critical issues. One efficient and accurate electronic structure method is the generalized gradient approximation to the Kohn–Sham density functional theory implemented using a plane‐wave basis set and atomic pseudopotentials. The marriage of the gradient‐corrected density functional approach with molecular dynamics, as pioneered by Car and Parrinello (R. Car and M. Parrinello, Phys Rev Lett 1985, 55, 2471), has been demonstrated to be capable of elucidating the atomic scale structure and dynamics underlying many complex systems at finite temperature. However, despite the relative efficiency of this approach, it has not been possible to obtain parallel scaling of the technique beyond several hundred processors on moderately sized systems using standard approaches. Consequently, the time scales that can be accessed and the degree of phase space sampling are severely limited. To take advantage of next generation computer platforms with thousands of processors such as IBM's BlueGene, a novel scalable parallelization strategy for Car–Parrinello molecular dynamics is developed using the concept of processor virtualization as embodied by the Charm++ parallel programming system. Charm++ allows the diverse elements of a Car–Parrinello molecular dynamics calculation to be interleaved with low latency such that unprecedented scaling is achieved. As a benchmark, a system of 32 water molecules, a common system size employed in the study of the aqueous solvation and chemistry of small molecules, is shown to scale on more than 1500 processors, which is impossible to achieve using standard approaches. This degree of parallel scaling is expected to open new opportunities for scientific inquiry. © 2004 Wiley Periodicals, Inc. J Comput Chem 16: 2006–2022, 2004

Gao, Xingfa; Yuan, Hui; Chen, Zhenling; Zhao, Yuliang

doi: 10.1002/jcc.20128pmid: 15473009

The possible isomers of a newly synthesized C141 molecule are calculated using MNDO, AM1, PM3, B3LYP/3‐21G, and B3LYP/6‐31G(d) methods. The geometry optimizations showed that the isomer 8‐8 has the lowest total energy in all 64 possible structures of C141. Unlike those of C130, C140, etc., the C141 8‐8 shows a new structure: two C70 side cages open (6.6) ring junctions located at the equator (instead of cap) area to create new chemical bonds for the bridge atom. Theoretical measurements of the average length of the long and short axes of C70 side cages in the C141 molecule reveal that when two C70 cages are connected with each other at the equators, their geometric shapes become more spherical compared with the pristine C70; this leads to a reduction of the molecular polarizability. Analysis of the local and global strain indicates that the global strain of C70 monomer in the C141 8‐8 is greatly reduced compared to the pristine C70. The stable C70 derivatives that are formed with reacted CC bonds in the equator area may put new insights into fullerene chemistry, in particular, for C70 to react with a large molecule. The results are discussed together with the experimental data. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 2023–2030, 2004

Cerqueira, Nuno M. F. S. A.; Fernandes, Pedro Alexandrino; Eriksson, Leif A.; Ramos, Maria João

doi: 10.1002/jcc.20127pmid: 15481089

This article focuses on the first step of the catalytic mechanism for the reduction of ribonucleotides catalyzed by the enzyme Ribonucleotide Reductase (RNR). This corresponds to the activation of the substrate. In this work a large model of the active site region involving 130 atoms was used instead of the minimal gas phase models used in previous works. The ONIOM method was employed to deal with such a large system. The results gave additional information, which previous small models could not provide, allowing a much clearer evaluation of the role of the enzyme in this step. Enzyme–substrate interaction energies, specific transition state stabilization, and substrate steric strain energies were obtained. It was concluded that the transition state is stabilized in 4.0 kcal/mol by specific enzyme–substrate interactions. However, this stabilization is cancelled by the cost in conformational energy for the enzyme to adopt the transition state geometry; the overall result is that the enzyme machinery does not lead to a rate enhancement in this step. It was also found that the substrate binds to the active site with almost no steric strain, emphasizing the complementarity and specificity of the RNR active site for nucleotide binding. The main role of the enzyme at the very beginning of the catalytic cycle was concluded to be to impose stereospecifity upon substrate activation and to protect the enzyme radical from the solvent, rather than to be an reaction rate enhancement. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 2031–2037, 2004

Mongan, John; Case, David A.; McCammon, J. Andrew

doi: 10.1002/jcc.20139pmid: 15481090

A new method is proposed for constant pH molecular dynamics (MD), employing generalized Born (GB) electrostatics. Protonation states are modeled with different charge sets, and titrating residues sample a Boltzmann distribution of protonation states as the simulation progresses, using Monte Carlo sampling based on GB‐derived energies. The method is applied to four different crystal structures of hen egg‐white lysozyme (HEWL). pKa predictions derived from the simulations have root‐mean‐square (RMS) error of 0.82 relative to experimental values. Similarity of results between the four crystal structures shows the method to be independent of starting crystal structure; this is in contrast to most electrostatics‐only models. A strong correlation between conformation and protonation state is noted and quantitatively analyzed, emphasizing the importance of sampling protonation states in conjunction with dynamics. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 2038–2048, 2004