bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanics study of myelin basic protein peptide 87‐118: Some local energy minima
Authors: Gilliom Richard D. , Stoner Gerald L.
Published: January 2005

Myelin basic protein (MBP) is the major extrinsic protein of the myelin sheath in the central nervous system. It is this protein that is destroyed in such demyelinating diseases as multiple sclerosis. We have examined the predicted structures of one segment of MBP using the molecular mechanics program ECEPP83 developed by Scheraga and co‐workers as modified by Chuman, Momany, and Schafer. We have focused upon a segment, 87‐118, containing the Pro‐Pro‐Pro sequence (residues 100–102), which has been predicted from standard algorithms to exist in a hairpin loop connecting anti‐parallel beta‐strands. Several local energy minima have been found and reported. Tripoline sequences are not rare in proteins, but their structure and function is still uncertain.
An algorithm for the simultaneous superposition of a structural series
Authors: Kearsley Simon K.
Published: January 2005

A procedure is delineated for finding the optimal superposition of a series of chemical structures. Quaternions are used to represent the absolute orientation of the structures–rotations of the structures need never be carried out explicitly. The Rational Function Optimization method is used to minimize a simultaneous superposition residual similar to the one given by Gerber and Müller. The robustness of the method is illustrated by comparing a series of conformations of a polyene carotenoid.
Automated conformational analysis: Directed conformational search using the A* algorithm
Authors: Leach Andrew R. , Prout Keith
Published: January 2005

A common requirement in conformational analysis is the identification of a molecule's lowest energy conformations. The application of the A* algorithm to this problem is examined. The algorithm uses heuristic information about the problem domain to direct the search and has been implemented in a system for performing automated conformational analysis. The method is detailed and sample results presented. Some limitations of the approach are identified.
A novel decomposition of torsional potentials into pairwise interactions: A study of energy second derivatives
Authors: Dinur U. , Hagler A. T.
Published: January 2005

A general method of analyzing intramolecular torsional potentials in terms of energy second derivatives that couple the rotating atoms is presented. The method offers a rigorous decomposition of the total torsional potential into pairwise (dihedral) interactions and enables one to derive nonbonded torsional interactions between 1–4 atoms as well as between more distant atoms and sites. The method is demonstrated on ethane, propane and acetaldehyde. It is shown that the 1–4 H…H dihedral potentials in ethane and propane are very similar, thereby supporting the notion of transferable force field potential functions. However, the dihedral potentials that are obtained differ from 1–4 potentials that are used in current force fields. Intramolecular three body effects are clearly seen in this method and are found to be relatively large for the dihedral interactions, although in the one case studied (propane) the overall effect on the methyl‐methyl interaction is negligible due to cancellation of terms. The analysis explicitly shows that the barrier in acetaldehyde is due mainly to the dihedral H…H interaction.
Structural effects of fluorine substitution in proteins
Authors: Gregory D. H. , Gerig J. T.
Published: January 2005

The consequences of substitution of fluorine for the para hydrogen of a phenylalanine residue in ribonuclease‐S were investigated by conformational energy calculations using the AMBER force field. Both the fluorine‐containing protein and the corresponding nonfluorinated material were subjected to conformational adjustment through energy minimization and the minimum energy structures so defined were compared. Fluorine substitution leads to small alterations in many atomic positions in the protein, with adjustments at at sites more than 0.5 nm from the fluorine appearing to be somewhat larger than those within the immediate vicinity of the fluorine. Several atoms proximate to the fluorine atom were observed to move toward the fluorine while others in the same vicinity move away. The greater bulk of the fluorine atom and the strongly different electronic properties of fluorine compared to hydrogen thus appear to be insufficient to cause a consistent, unidirectional change in nearest‐neighbor interactions upon introduction of a fluorine atom into a protein structure. Virtually all changes in atomic positions that are predicted by these calculations would be barely detectable by a crystallographic study with a resolution of 0.2 nm.
Molecular silverware. I. General solutions to excluded volume constrained problems
Authors: Blanco Mario
Published: January 2005

General mathematical solutions to excluded volume constrained problems in computational chemistry are reported. The solutions have been used to create a new family of molecular modeling algorithms to facilitate the study of molecular interactions in condensed phases. The new algorithms, collectively known as Molecular Silverware, are for the most part interactive and designed for packing, solvating, and sampling molecules embedded in simple or complex topological environments. Multifolded, disconnected, or porous molecular structures are permitted. Molecular Silverware assists the preparation of Monte Carlo and molecular dynamics simulations at a small fraction of the total simulation time. Primary targets for applications include the study of molecular recognition mechanisms and the selective binding of DNA, RNA, peptides, saccharides and other biopolymers in solution as well as the prediction of phase separation behavior and physical properties of non‐crystalline condensed phases such as bulk polymers, polymer blends, organic liquids, membranes, micelles, gels, crosslinked networks, glasses, and amorphous heterogeneous catalysts. As a result of this new approach to excluded volume constraints, the computer simulation of noncrystalline condensed phases is no longer hampered by the lack of a general and efficient method for the creation and configurational sampling of small and large molecular assemblies at high densities.
Comments on the characteristic polynomial of a graph
Authors: Balasubramanian K.
Published: January 2005

Several unique advantages of the Le Verrier–Fadeev–Frame method for the characteristic polynomials of graphs over the method proposed by Zivković recently based on the Givens–Householder method are described. It is shown that the Givens–Householder method proposed by Zivković, by itself fails for directed graphs, signed graphs, and complex nonhermetian graphs requiring extensive modifications to the Householder algorithm through the double + random shift QR procedure requiring more computations than claimed. Furthermore, the QR procedure does not always converge and requires random shifts. To the contrary, it is shown that the Le Verrier–Fadeev–Frame method does not require any such modifications or random shifts and takes less total CPU times when both algorithms are run using vector processors. Hence it is demonstrated that the Le Verrier–Frame algorithm is efficient and superior in its universal and direct applicability to all graphs requiring no further modifications (directed, signed, and complex).
On a proposed radiation‐induced polaronic hole in silicon dioxide
Authors: Rao P. S. , McEachern R. J. , Weil J. A.
Published: January 2005

Ab‐initio self‐consistent‐field molecular‐orbital (SCF MO) Hartree–Fock (HF) calculations using the STO‐3G, 6‐31G, and 6‐31G* basis sets, were performed to model quasi‐tetrahedral silicon species in silicon dioxide. Mostly nine‐atom clusters, [Si(OH)4]qt, with charge number qt = 0 or + 1, were studied. The positions of the Si and O atoms were varied to achieve minimum total energies, while the protons were held fixed in the O‐(neighboring)Si direction to simulate the rigid crystal surroundings. The α‐quartz‐type local symmetry C2 was found to be retained for the neutral cluster, but not for the ionic one. The unrestricted HF calculations indicate that the latter paramagnetic centre, (qt = +1), has its spin population almost entirely on one short‐bonded oxygen ion bonded weakly to its neighboring Si, and is quite high in energy (9.55 eV with 6‐31G) compared to the diamagnetic centre (qt = 0). The ionization energy is much higher than the self‐trapping potential of the polaronic hole, a fact which may account for the failure so far to observe a [SiO4]+1 center in quartz by means of continuous‐wave electron paramagnetic resonance spectroscopy. Calculations on the [SiO4]+1 center agree well with ultraviolet spectra, and with the [hole portion of a] proposed radiation‐induced exciton in quartz. The hole in [Si(OH)4]+1 can be shifted from a short‐bonded to a long‐bonded oxygen to give the excited state [Si(OH)4]es+1. Conclusions reached with the nine‐atom clusters were confirmed by a series of calculations on the extended model [Si(OSiH3)4]qt. Comparisons with the known isoelectronic species [AlO4]0 were carried out.
Free energy difference calculations by thermodynamic integration: Difficulties in obtaining a precise value
Authors: Mitchell Michael J. , McCammon J. Andrew
Published: January 2005

Free energy difference calculations have been performed by the “slow growth” method of thermodynamic integration of the AMBER 3.0 molecular dynamics program for the mutation of a conformationally restricted threonine dipeptide, N‐acetyl threonyl‐N‐methylamide, to the corresponding alanyl dipeptide. By varying the total simulation length, it has been determined that precise free energy values are obtained only for simulations of greater than 100 ps total simulation time length. By varying the starting configurations for simulations of the same length, it has been determined that averaging the free energies obtained from shorter simulations may not give precise answers. Possible reasons for this behavior are discussed.
OPKINE, a multipurpose program for kinetics
Authors: Pla F. Perez , Baeza J. J. Baeza , Ramos G. Ramis , Palou J.
Published: January 2005

The program OPKINE is presented for the study of reaction mechanisms and multicomponent analysis in dynamic conditions. This program is written in FORTRAN‐77 for IBM 30/90 and VAX 8300 computers, and permits the simultaneous evaluation of both rate constants and initial reagent concentrations or, alternatively, rate constants and sensitivities. Up to 20 kinetic curves, with up to 400 points each, can be treated to evaluate up to 40 parameters. Integration of the system of differential equations is performed by means of the Runge–Kutta–Fehlberg method. OPKINE is provided with the Simplex, and modified versions of the Davidon–Fletcher–Powell and Gauss–Newton–Marquardt optimization methods. A Monte Carlo procedure to search for the seeds is also available. Simulated experiments have been used to check the performances of the program. Complex kinetic mechanisms and mixtures of a large number of analytes can be managed with good results.
Incorporating solvent and ion screening into molecular dynamics using the finite‐difference Poisson–Boltzmann method
Authors: Sharp Kim
Published: January 2005

The finite difference method for solving the Poisson–Boltzmann equation is used to calculate the reaction field acting on a macromolecular solute due to the surrounding water and ions. Comparisons with analytical test cases indicate that the solvation forces can be calculated rapidly and accurately with this method. These forces act to move charged solute atoms towards the solvent where they are better solvated, and to screen interactions between charges. A way of combining such calculations with conventional molecular dynamics force fields is proposed which requires little modification of existing molecular dynamics programs. Simulations on the alanine dipeptide show that solvent forces affect the conformational dynamics by reducing the preference for internal H‐bonding forms, increasing theR‐alpha helix preference and reducing transition barriers. These solvent effects are similar to previous explicit solvent simulations, but require little more computation than vacuum simulations. The method should scale up with little increase in computational cost to larger molecules such as proteins and nucleic acids.
Chemical shift bond derivatives for molecules containing first‐row atoms
Authors: Chesnut D. B. , Wright D. W.
Published: January 2005

The primary and secondary first and second derivatives of the NMR isotropic chemical shift with respect to bond length modification have been calculated in the gauge invariant atomic orbital (GIAO) perturbed Hartree–Fock approach for some 177 first‐row nuclei in 63 molecules using the mixed basis heavy:6–311G(d)/hydrogen:4–31. The shift derivative with respect to multiple bond length changes correlates linearly with the shift itself while changes involving single bonds behave differently. Agreement between experimental derivatives and those calculated theoretically is good but the calculations show that second derivatives as well as both types of secondary effects cannot always be neglected. The correlation between the shift derivative and the isotropic shift indicates an exponential variation of the chemical shift with bond length near the vicinity of the equilibrium structure for multiple bonds.
MRD‐CI potential surfaces using balanced basis sets. VI. Correlation of bond order with bond function composition for first‐row diatomic molecules
Authors: Barclay V. J. , Wright James S.
Published: January 2005

This article presents theoretical calculations on bond energies for the first‐row diatomics C2, CN, CO, CF, N2, NO, NF, O2, FO, and F2, which vary in bond order from one to three. The atomic‐centered basis functions are systematically augmented with bond functions (BFs), which range in composition from (sp) to 2(spd), to determine the basis set which yields a dissociation energy closest to the experimental De. A strong correlation is found to exist between the bond order and the number of BFs required in the optimum basis set. Based on these results, we are able to predict the optimum composition of the BF basis which should be added to a DZP‐quality AO basis set for a case in which only the bond order is known. These optimized BF basis sets are shown in the accompanying article to give more accurate potential curves than larger basis sets without bond functions.
Parametrization of calcium binding site in proteins and molecular dynamics simulation on phospholipase A2
Authors: Shiratori Yasuhiko , Nakagawa Setsuko
Published: January 2005

The empirical energy parameters for a calcium ion and its ligands in proteins were determined within a pairwise additive framework. The interaction energies of Ca2+‐water, Ca2+‐peptide group and Ca2+‐carboxyl group systems were calculated using the ab initio molecular orbital method with basis sets of double zeta quality including polarization or diffuse functions. The resulting potential energy surfaces served as references for the determination of the nonbonded parameters in the empirical energy function. The nonadditive corrections for the Ca2+‐ligand pair potentials are incorporated implicitly in the nonbonded paremeters by treating three‐body (1:2 complex) or seven‐body (1:6 complex) systems in reference calculations. Ligand polarizations induced by Ca2+ are estimated from the partial atomic charges of two‐body (1:1 complex) systems. The charge sets were determined by scaling so as to reproduce the reference potential energy surfaces. The newly determined parameter set was used in a stochastic boundary molecular dynamics simulation of phospholipase A2. The solvated structure of the Ca2+‐binding site obtained from an X‐ray crystallographic study is well reproduced by the parameter set.
Comparison of AM1 and ab initio calculation of the carbon‐carbon bond rotation in ethylene glycol diacetate
Authors: Fagerburg David R.
Published: January 2005

The C‐C glycol bond rotational energy in ethylene diacetate as a polyester model was compared using the semiempirical method AM1 and an ab initio method with an STO‐3G basis set. The results were qualitatively much different depending on the method used. Ab initio calculations showed the expected minima at 180 and near 60 (69.6) degrees dihedral angle with maxima at 0 and 120 degrees. The AM1 rotational curve indicated an apparent minimum at a 90 degree dihedral angle, a shallow, apparent maximum at 180 degrees and an apparent maximum at 0 degrees which could not be confirmed as minima or maxima via frequency calculations. Ethylene diacetate analog compounds with one or two ester oxygens replacing methylene group(s) gave curves with AM1 having the general shape for ethylene diacetate by the ab initio method, indicating a parameterization problem for the otherwise very useful AM1 to correctly handle a compound with only two carbons between the two electronegative oxygen atoms thus rendering this method currently unsuitable for examination of rotational energy barriers of such polyester model compounds.
The half‐projected Hartree–Fock model for computing thermally “forbidden” pericyclic reactions
Authors: Olivella Santiago , Salvador José
Published: January 2005

The possible use of a half‐projected Hartree–Fock (HPHF) wavefunction correlating a single pair of electrons is investigated in relation with the computation of potential energy hypersurfaces associated to pericyclic reactions of systems with an even number of electrons, in which the orbital configuration of the lowest‐energy singlet state is not conserved during the course of the reaction. The results of calculations, within the framework of the MINDO/3 Hamiltonian, for eleven stationary points on the potential energy hypersurfaces of three prototypical thermally “forbidden” pericyclic reactions indicate that, in general, the HPHF model provides a geometrical and energetical description that is equivalent to that obtained from a conventional two‐configuration self‐consistent‐field approach.
Determination of molecular topology and atomic hybridization states from heavy atom coordinates
Authors: Meng Elaine C. , Lewis Richard A.
Published: January 2005

A method is presented for the derivation of hybridization states and connectivity within molecules from the atomic numbers and coordinates of heavy atoms. The algorithm utilizes bond length data from studies of the Cambridge Structural Database (Allen et al., J. Chem. Soc. Perkin Trans. II, S1, (1987)). The program, IDATM, is useful for processing input to hydrogen‐adding routines and molecular mechanics programs, as it minimizes the amount of manual preprocessing required. IDATM has been tested on a range of crystallographically determined structures, including poorly determined structures, with a successful assignment of hybridization for over 99% of the atoms in the set.
Calculations of molecular vibrational frequencies using semiempirical methods
Authors: Coolidge Michael B. , Marlin John E. , Stewart James J. P.
Published: January 2005

MINDO/3, MNDO, AM1, and PM3 calculations of molecular vibrational frequencies are reported for 61 molecules. All techniques were applied to both well‐behaved and badly behaved systems. Overall, MINDO/3 and MNDO were found to contain rather large errors whereas AM1 and PM3 were relatively accurate. Since no technique does well for all molecules, the technique used should be chosen based on the molecular vibration of interest. In general, AM1 and PM3 together provide fairly accurate results.
New method for the computation of ionic distribution around rod‐like polyelectrolytes with the helical distribution of charges. I. General approach and a nonlinearized Poisson–Boltzmann equation
Authors: Rashin Alexander A. , Malinsky Joseph
Published: January 2005

This article is a first step in an attempt to reevaluate the relative role of different contributions to the energetics of DNA in salt solutions. To identify individual terms yielding such contributions a new derivation is given of the generalized Poisson–Boltzmann equation, which includes correlation effects, and explicitly shows terms ignored in the regular Poisson–Boltzmann approach. A general method based on the Boundary Element Technique is discussed, which can be used to evaluate these terms in the next steps of the reevaluation. An implementation of this method for the solution of the nonlinear Poisson–Boltzmann equation is described in detail, and is used to compute the ionic atmosphere around DNAs modeled as cylinders with helical distributions of charges. In the B‐type DNA models, it is found that the ion densities in the minor and major grooves near the DNA surface differ by up to threefold. This difference is ca. 10‐fold for Z‐type DNA models. There are 20–25% differences in the magnitude of the maximum ionic charge density between DNA models of the same type. The addition of excess salt (up to 0.15 M) changes this maximum by only 10–15%. This change is not proportional to the concentration of excess salt. The contributions of different factors to the stabilization of alternative forms of DNA are evaluated. These factors are: (1) interactions between the phosphates, (2) interactions of phosphates with water, (3) interactions of phosphates with the ionic cloud, (4) interactions within the ionic cloud, (5) entropy of the ionic cloud. It is found that regardless of large variations in the counterion distributions around different DNAs, energetic contributions from these distributions are similar (−12.65 ± 0.6 kcal/mol · cell). The calculated change in stabilization per unit cell of models of B and Z‐type DNAs due to 0.15 M excess NaCl is only −0.56 ± 0.02 kcal/mol, indicating no tendency toward B‐Z transition in this concentration range. Significantly larger variations of the order of 10 kcal/mol per unit cell can result from factors 1–2. Possible effects of the realistic DNA‐solvent boundaries on the energetics of DNA solutions are discussed.
Host‐guest preorganization and complementarity: A molecular mechanics and molecular dynamics study of cation complexes of a cyclic urea‐anisole spherand
Authors: Maye P. V. , Venanzi C. A.
Published: January 2005

Molecular mechanics and molecular dynamics calculations were carried out in vacuo for 1 and for the complexes of 1 with alkali metal cations and t‐BuNH. The calculations identify perching and nesting conformations of the complexes not available from X‐ray data. For the Li+ −1 complex, the MD simulations identify a new global minimum not found by the molecular mechanics calculation. In general, the net favorable ion‐spherand complexation energy is due to the offset of the unfavorable reorganization energy of the spherand by the overwhelmingly favorable electrostatic component of the ion‐spherand interaction energy. The host is least preorganized for the binding of Li+ and, even in its complexed conformation, presents the least steric complementarity to this ion. The complexation energy becomes significantly more favorable due to a large increase in the electrostatic complementarity of the ion binding site when the spherand adopts its complexed conformation. Correction of the calculated complexation energy by the experimental free energy of ion aqueous desolvation leads to results in line with the findings of Cram and co‐workers that K+ is the most, and Li+ the least, favorably bound by 1.
Vectorization of the general Monte Carlo classical trajectory program VENUS
Authors: Hu Xiche , Hase William L. , Pirraglia Tony
Published: January 2005

The general chemical dynamics computer program VENUS is used to perform classical trajectory simulations for large polyatomic systems, with many atoms and complicated potential energy functions. To simulate an ensemble of many trajectories requires a large amount of CPU time. Since each trajectory is independent, it is possible to parallel process a large set of trajectories instead of processing the trajectories by the conventional sequential approach. This enhances the vectorizability of the VENUS program, since the integration of Hamilton's equations of motion and the gradient evaluation, which comprise 97.8% of the CPU, can each be parallel processed. In this article, the vectorization and ensuing optimization of VENUS on the CRAY‐YMP and IBM‐3090 are presented in terms of both global strategies and technical details. A switching algorithm is designed to enhance the vector performance and to minimize the memory storage. A performance of 140 MFLOPS and a vector/scalar execution rate ratio of 10.6 are observed when this new version of VENUS is used to study the association of CH3 with the H(Ar)12 cluster on the CRAY‐YMP.
Efficient search for all low energy conformations of polypeptides by Monte Carlo methods
Authors: von Freyberg Berthold , Braun Werner
Published: January 2005

The Metropolis Monte Carlo method has been added to the program FANTOM for energy refinement of polypeptides and proteins using a Newton–Raphson minimizer in torsion angle space. With this extension, different strategies for global minimization of the semiempirical energy function ECEPP/2 by various temperature schedules and restriction of conformational space were tested for locating local minimum conformations with low energy of the pentapeptide Met‐enkephalin. In total, 1881 conformations below −10 kcal/mol were found. These conformations could be represented by 77 nonidentical conformations which were analysed for their pattern of hydrogen bonds, types of tight turn, pairwise root‐mean‐square‐deviation (rmsd), Zimmermann codes and side chain conformations. All low energy conformations below −10.4 kcal/mol show strong similarity to the global minimum conformation in the backbone structure.
Stabilities of small Ben and Bn clusters (4 ≤ n ≤ 8) by vibrational analysis
Authors: Kato Hiroshi , Tanaka Eishi
Published: January 2005

The stabilities Ben and Bn clusters (4 ≤ n ≤ 8) based on the vibrational analysis were investigated by ab initio MO calculations. The computations were performed by using a 3‐21G basis set at the R(U)HF level and at the R(U)MP4 level with the HF optimized structures. Spin‐multiplicities were also considered up to quintet states (n ≤ 7). Of the 120 species that were treated, half of them were considered stable and some of these stable species were obtained by the deformations of transition state and unstable species, following the imaginary normal modes. The transformation barrier between the transition state species and corresponding stable ones was presented. It was found that there were two types of stable clusters: (1) a low symmetry species with lower frequencies and lower geometrical change barriers and (2) a high symmetry one with higher frequencies. The former type was considered as a structural “soft” species and the latter as a “hard” species.
The number of spanning trees in buckminsterfullerene
Authors: Brown T. J. N. , Mallion R. B. , Pollak P. , de Castro Branca R. M. , Gomes J. A. N. F.
Published: January 2005

The theorem of Gutman et al. (1983) is applied to calculate the number of spanning trees in the carbon‐carbon connectivity‐network of the recently diagnosed C60‐cluster buckminsterfullerene. This “complexity” turns out to be approximately 3.75 × 1020 and it is found necessary to invoke the device of modulo arithmetic and the “Chinese Remainder Theorem” in order to evaluate it precisely on a small computer. The exact spanningtree count for buckminsterfullerene is 375 291 866 372 898 816 000, or, 225 × 34 × 53 × 115 × 193. A “ringcurrent” calculation by the method of McWeeny may be based on any desired one of this vast number of spanning trees.
A fully three‐dimensional finite element method calculation for the vibrational levels of H2O and D2O
Authors: Neto J. J. Soares , Linderberg Jan
Published: January 2005

A finite element method approach for solving the three‐dimensional Schrödinger equation expressed in hyperspherical coordinates is applied to the calculation of rovibrational states of H2O and D2O. Comparisons to experimental values and other theoretical calculations are offered.
A comparison of distance geometry and molecular dynamics simulation techniques for conformational analysis of β‐cyclodextrin
Authors: Wertz David A. , Shi Chen‐Xi , Venanzi Carol A.
Published: January 2005

Distance geometry and molecular dynamics simulation techniques were compared in their ability to search the conformational potential energy surface of β‐cyclodextrin. Structures generated by the DISGEO program were minimized using three different atomic point charge sets. Some of these structures were used as starting points for molecular dynamics simulation in vacuo at 298K. The distance geometry results showed that the global features of the conformational potential energy surface were generally independent of the point charge set. The distance geometry technique was able to find structures of lower energy than those obtained by direct minimization of the X‐ray or neutron diffraction structures. However, the molecular dynamics simulation technique was consistently able to find structures of lower energy than those generated by distance geometry. Root mean square fit of the trajectory structures to the starting structure showed that the simulation allowed the molecule to explore regions of the potential energy surface in the neighborhood of the starting structure. Both the distance geometry and molecular dynamics simulation techniques showed that β‐cyclodextrin can adopt a wide range of conformations in the gas phase and that these conformations are much less symmetrical than the crystalline structure.
Ab initio and molecular mechanics calculations on imine derivatives: A study of the rotational barriers and the development of MM2 parameters
Authors: Kontoyianni Maria , Hoffman Andrew J. , Bowen J. Phillip
Published: January 2005

The application of molecular mechanics methods for the study of structures has become a standard approach to conformational analysis. The MM2 force field has been extended to include imines. In general, a diverse group of aliphatic and aromatic imine structures can now be treated. The rotational energy profiles and barriers to N‐substituted imines about the Csp2Csp2 single bonds adjacent to CN functional group were calculated via ab initio MO theory. Information obtained from the quantum mechanical calculations at the 3‐21G, 6‐31G*, and MP4/6‐31G* //6‐31G* levels was used both to study the phenomena involved and to parameterize MM2. The syn‐anti isomerization was also studied, and the mechanistic pathways have been evaluated. In cases where the comparison with experimental data can be made, the agreements are good.
Kinetic effects of multiple charge modifications in enzyme‐substrate reactions: Brownian dynamics simulations of Cu, Zn superoxide dismutase
Authors: Sines Jacqueline J. , McCammon J. Andrew , Allison Stuart A.
Published: January 2005

We used Brownian dynamics simulations of substrate O encounters with the enzyme bovine erythrocyte Cu, Zn superoxide dismutase (SOD) to study the effects of multiple charge modifications in the enzyme on the kinetics of its diffusion‐controlled reaction. When the charges of two or three residues were changed, the calculated rate consant relative to that for the unmodified enzyme was usually found to be the product of relative rate constants for the enzymes with the corresponding single‐site changes. This “multiplicativity” rule may be useful in the design of enzymes that operate with diffusion‐controlled kinetics. Residues that deviate from the general rule are found in the active site channel of SOD, and the origin of these deviations is considered.
Correlation and solvation effects. IV. A systematic analysis of the influence of cavity size and shape on solvation properties in the polarizable continuum model with electron correlation
Authors: del Valle F. J. Olivares , Aguilar M.A.
Published: January 2005

From the standpoint of models that use a polarizable continuum to represent the solvent in studying the phenomenon of solvation, a systematic and detailed analysis is made of the influence of the cavity size and shape on calculated energies. The solute is represented by its ab initio wavefunction, and the electronic part of the solvation energy is calculated including terms that take into account electron correlation up to third order. The analysis shows the convenience of modeling the cavity according to considerations of homogeneity, which are based fundamentally on how the solute wavefunction is constructed, i.e., the basis set used.
A systematic ab initio study of the group V trihalides MX3 and pentahalides MX5 (M = PBi, X = FI)
Authors: Breidung Jürgen , Thiel Walter
Published: January 2005

Ab initio calculations using effective core potentials and polarized split‐valence basis sets are reported for the title compounds. The calculated geometries, vibrational frequencies, infrared intensities, harmonic force fields, dipole moments, relative energies, and barriers to pseudorotation are compared with the available experimental data for the known molecules. Predictions are made for those pentahalides that are still unknown. Trends in the calculated properties are identified and discussed.
Probing the conformational space available to inhibitors in the thermolysin active site using Monte Carlo/energy minimization techniques
Authors: Guida Wayne C. , Bohacek Regine S. , Erion Mark D.
Published: January 2005

The conformational space available to four inhibitors of the bacterial enzyme thermolysin has been searched in the enzyme binding site using a method that combines Monte Carlo type techniques with energy minimization for exploration of the conformational potential energy hypersurface. Molecular mechanics methodology using the AMBER force field was employed for computation of the molecular energetics. Solvation energies were also included in the calculations by employing a technique that estimates hydration energies based on the exposed solvent accessible surface area for each atom of the inhibitor and active site. It was found that in each case, the crystallographically observed conformation was among the low energy conformers discovered. In fact, in three of the calculations it was the lowest energy conformation. The methodology described in this article is expected to be quite useful for studies involving computer aided design and evaluation of enzyme inhibitors.
Free energy perturbation calculations involving potential function changes
Authors: Ferguson David M. , Pearlman David A. , Swope William C. , Kollman Peter A.
Published: January 2005

The solvation free energies of thymine and adenine were calculated using free energy methods to examine the effect of applying Lennard–Jones 6‐12 and 10‐12 perturbations to the hydrogen‐bonding groups. The calculations were performed using a new free energy algorithm developed for the AMBER 4.0 program package that allows an interaction described by a Lennard–Jones 6‐12 potential to be changed into one described by a hydrogen bond 10‐12 potential. The algorithm applied allows this change to occur smoothly without the generation of more extrema on the potential surface. Results using this algorithm have been compared with those determined using the standard AMBER 3.0 Revision A program package, which provides for 6‐12 to 6‐12 parameter perturbations only. We have also developed a procedure to perform pyrimidine to purine nucleoside mutations to calculate the relative free energies of solvation directly. The theoretical results are compared to experimental energies derived from solvation and vaporization data taken from the literature. The free energies calculated using the new algorithm show good agreement with the derived experimental values. This is also true for the calculations that employ the 6‐12 function only, but with 6‐12 parameters modified to reflect the correct hydrogen‐bonding interactions. However, perturbation of the “standard” 6‐12 parameters without changing the functional form proves to be less effective in determining solvation free energies correctly, and demonstrates the importance of accurate hydrogen bond descriptions in free energy simulations.
Parallelization of quantum mechanical integral calculations
Authors: Kindermann S. , Michel E. , Otto P.
Published: January 2005

In ab initio Hartree—Fock crystal orbital calculations of chemical and physical properties of polymers, the huge number of two‐electron integrals restricts the size of the elementary cell. Therefore, the question arises how the storage and computation resources of modern parallel supercomputers can be exploited. In this work, we report the parallelization of the one‐ and two‐electron integral programs, respectively, for the parallel computer SUPRENUM. A short description of the hardware and software environment of this supercomputer is given. The results are discussed with respect to speed‐up and efficiency.
Vinyloxyborane and its isomers. An ab initio study of the C2H5BO potential energy surface, the barrier to 1,3‐shifts in β‐ketoboranes, and the mechanism of the carbonylation reaction of boranes
Authors: Ibrahim Mustafa R. , Bühl Michael , Knab Reinhard , Schleyer Paul Von Rague
Published: January 2005

Vinyloxyboranes, CH2CH;O;BR2, are shown by ab initio molecular orbital theory to be more stable than the isomeric β‐aldoboranes, R2BCH2CHO, by ca. 19 kcal/mol. The MP2/6‐31G*/6‐31G* + ZPE barrier for the [1,3] boron shift is only 10.9 kcal/mol (R  Me) relative to the aldoborane. Other C2H5BO isomers (β‐ketoboranes, boraepoxides and organoboron oxides), which are related to the proposed stages in the carbonylation reaction of boranes, are shown to be plausible intermediates. However, some of the computed barriers for methyl group migrations are unrealistically large, up to ca. 63 kcal/mol.
Precision of free energies calculated by molecular dynamics simulations of peptides in solution
Authors: Hermans Jan , Yun R.H. , Anderson Amil G.
Published: January 2005

Errors in free energies for molecular replacement and for conformation change of a small model peptide have been determined empirically by repeated simulations from different starting points. All calculations have been done using thermodynamic integration, in which the system's potential energy is coupled to a parameter λ, that is increased or decreased by a small amount at each step of the simulation. The effects of several factors that may alter the precision are evaluated. These factors include: the length of the simulation, the dependence of the potential energy on λ, the use of conformational restraints, and their magnitude and form. The methods used for restraint and conformational forcing are described in detail. The free energy change, calculated as the mean from several successive simulations with alternately increasing and decreasing λ, is found to be independent of the length of the simulations. As expected, longer simulations produce more precise results. The variation of the calculated free energies is found to consist of two parts, a random error and a systematic hysteresis, i.e., a dependence on the direction in which λ changes. The hysteresis varies as the inverse of the length of the simulation and the random error as the inverse square root The advantage of the use of a different (nonlinear) dependence of the attractive and repulsive parts of the nonbonded potential energy on the coupling parameter when “creating” particles in solution is found to be very large. This nonlinear coupling was found to be superior to the use of linear coupling and a nonlinear change of the coupling parameter with the simulation time. The hysteresis in conformational free energy calculations is found to increase markedly if too weak a forcing restraint is chosen. It is shown how to deconvolute the contribution of a torsional restraint from the dependence of the free energy on a torsion angle.
Relative log P and solution structure for small organic solutes in the chloroform/water system using monte carlo methods
Authors: Dunn William J. , Nagy Peter I.
Published: January 2005

Relative log P values of dimethylether to methanol and dimethylamine to methylamine were calculated in the chloroform/water system using Monte Carlo simulations and statistical perturbation theory. Correct ordering of the calculated relative log Ps was obtained for the two pairs although the method leads to an overestimation of these values. In aqueous solution, both dimethyl ether and dimethylamine solutes are proton acceptors forming a single hydrogen bond to water. Dimethylamine forms a stable NH‐Ow hydrogen bond while the water hydrogen is poorly localized in the OH‐Ow bond to the ether. In chloroform, the solvent molecules are less ordered around the solutes than was found around methanol and methylamine.
Structural studies of aromatic amines and the dna intercalating compounds m‐amsa and o‐amsa: Comparison of mndo, am1, and pm3 to experimental and ab initio results
Authors: Smith Douglas A. , Ulmer Charles W. , Gilbert Matthew J.
Published: January 2005

The ability of the MNDO, AM1, and PM3 semiempirical methods to reproduce pyramidalization at the nitrogen in 15 aromatic amines has been examined and compared to experimental and other theoretical results. AM1 consistently gives the best agreement. We have therefore reexamined the DNA intercalating compounds m‐AMSA and o‐AMSA using AM1.
MO‐Studies of enzyme reaction mechanisms. I. Model molecular orbital study of the cleavage of peptides by carboxypeptidase A
Authors: Alex Alexander , Clark Timothy
Published: January 2005

Ab initio and semiempiridal (AM1) molecular orbital theory has been used to model the cleavage of formamide at the active site of carboxypeptidase A. The model active site consists of a zinc dication coordinated to two imidazoles, an acetate, a water with a hydrogen‐bonded formate, and a formamide molecule as model substrate. AM1 has been compared with ab initio theory for the coordination of water and formamide to Zn++ and found to give excellent energetic results. The course of the amide cleavage was therefore calculated with AM1. The first step of the reaction is the dissociation of the zinc‐coordinated water to give an active ZnOH+ species. The remote formate acts as proton acceptor. This process has an activation energy of only 4.6 kcal mol−1. The next and rate‐determining step is the concerted addition of the ZnOH+ moiety to the formamide CO bond. The ZnO distance in the transition state is more than 3 Å. In four further steps, the amide nitrogen is protonated and the CN bond cleaved. The net activation energy for the entire process is 15.5 kcal mol−1 relative to the active site model and 19.6 kcal mol−1 relative to the most stable point on the calculated reaction profile.
Vibrational Stark effect: Theoretical determination through the semiempirical AM1 method
Authors: Martí Josep , Lledós Agustí , Bertrán Juan , Duran Miquel
Published: January 2005

The vibrational Stark effect of a series of small molecules has been calculated by means of the semiempirical AM1 method through addition of the electron–field interaction term in the one‐electron Hamiltonian. Optimized geometrical parameters along with harmonic frequencies and line intensities are determined for different strengths of the applied uniform electric field. The perturbed spectra are compared with theoretical studies carried out at the ab initio level and with experimental results. The vibrational Stark effect of the retinal molecule is also computed, showing that this kind of study is feasible in systems of biochemical interest. © 1992 by John Wiley & Sons, Inc.
Theoretical studies of organometallic compounds. II. All electron and pseudopotential calculations of M(CH3)nCl4 − n (M = C, Si, Ge, Sn, Pb; n = 0–4)
Authors: Jonas Volker , Frenking Gernot , Reetz Manfred T.
Published: January 2005

The performance of effective core potentials (ECP) for the main group elements of group IV has been studied by calculating the geometries and reaction energies of isodesmic reactions for the molecules M(CH3)nCl4 − n (M = C, Si, Ge, Sn, Pb; n = 0–4) at the Hartree–Fock level of theory. The results are compared with data from all electron calculations and experimental results as far as available. The all electron calculations were performed with a 3‐21G(d) and a 6‐31G(d) basis set for Si, a (43321/4321/41) basis set for Ge, and a (433321/43321/431) basis set for Sn. For the ECP calculations the potentials developed by Hay and Wadt with a configuration (n)sa(n)pb and the valence basis set (21/21), extended by a set of d functions, are employed. © 1992 by John Wiley & Sons, Inc.
Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models
Authors: Miyamoto Shuichi , Kollman Peter A.
Published: January 2005

An analytical algorithm, called SETTLE, for resetting the positions and velocities to satisfy the holonomic constraints on the rigid water model is presented. This method is still based on the Cartesian coordinate system and can be used in place of SHAKE and RATTLE. We implemented this algorithm in the SPASMS package of molecular mechanics and dynamics. Several series of molecular dynamics simulations were carried out to examine the performance of the new algorithm in comparison with the original RATTLE method. It was found that SETTLE is of higher accuracy and is faster than RATTLE with reasonable tolerances by three to nine times on a scalar machine. Furthermore, the performance improvement ranged from factors of 26 to 98 on a vector machine since the method presented is not iterative. © 1992 by John Wiley & Sons, Inc.
MNDO parameters for helium: Optimization, tests, and application to endohedral fullerene—helium complexes
Authors: Kolb Matthias , Thiel Walter
Published: January 2005

MNDO parameters for helium are derived from an optimization that employs only atomic and diatomic reference data. Comparisons with published high‐level ab initio results indicate that MNDO correctly predicts the existence of covalently bonded helium compounds and normally reproduces the geometries of these small charged molecules reasonably well. Endohedral fullerene–helium complexes and the transition states for their formation are studied for C60, C60, and C. The calculated barriers are discussed and compared with those for the passage of helium through C6H6, C6H, and C6H. © 1993 John Wiley & Sons, Inc.
Ab initio study of the ground and excited states of HCP and its isomer HPC
Authors: Goldstein Elisheva , Jin Suqian , Carrillo M. Robyn , Cave Robert J.
Published: January 2005

The potential energy surface of HCP converting to HPC in its ground electronic state has been investigated with ab initio methods at levels up to MP2/6‐311G**//MP4/6‐311G** as well as TZV + + ** CASSCF. All geometries are fully optimized and compare favorably to previous theoretical and experimental values. The HCP molecule is predicted to be 85.4 kcal/mol lower in energy than its linear isomer at the‐MP2/6‐31G*//MP2/6‐31G* level. The energy barrier for hydrogen rearrangement is found to be merely 2.3 kcal from the HPC end. CASSCF studies were initiated to clarify the low barrier and lent support to a flat surface as HPC converts to stable, linear HCP at the TZV + + ** level. CASSCF also predicts that HPC is unstable with respect to bending. Harmonic vibrational frequencies for HCP results in 5% accuracy or better. A bent triplet is found to be the lowest excited state using the CASSCF method. © 1993 John Wiley & Sons, Inc.