bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of Artificial Intelligence to the conformational analysis of strained molecules
Authors: Leach Andrew R. , Prout Keith , Dolata Daniel P.
Published: January 2005

An algorithm for predicting the conformations of strained molecules using Artificial Intelligence techniques is described and illustrated with some typical examples.
A conformational study of cocaine and its diastereomers
Authors: Villar Hugo O. , Loew Gilda H.
Published: January 2005

A conformational study of cocaine and its three diastereomers, pseudococaine, allococaine, and allopseu‐dococaine was carried out using molecular mechanics and quantum mechanical semiempirical techniques. Molecular dynamics simulations were performed at high temperature to scan their conformational space. Additional molecular dynamics at 312 K were used to explore the conformational flexibility of the compounds around the minimum energy conformation at physiologically relevant temperatures. The AM1 technique was used to refine the description of the minimum energy structures obtained with the molecular mechanics technique and to compute the electronic properties of cocaine and its diastereoisomers. Comparison of the results obtained with previous NMR and X‐ray structural data was carried out. The structural information obtained was then used to discuss some aspects of the pharmacology of cocaine and other compounds that bind at the site recognized by it on the dopamine transporter.
The MM3 force field for amides, polypeptides and proteins
Authors: Lii Jenn‐Huei , Allinger Norman L.
Published: January 2005

The potential functions for simple amides, several peptides and a small protein have been worked out for the MM3 force field. Structures and energies were fit as previously with MM2, but additionally, we fit the vibrational spectra of the simple amides (average rms error over four compounds, 34 cm−1), and examined more carefully electrostatic interactions, including charge‐charge and charge‐dipole interactions. The parameters were obtained and tested by examining four simple amides, five electrostatic model complexes, two dipeptides, six crystalline cyclic peptides, and the protein Crambin. The average root‐mean‐square deviation from the X‐ray structures for the six cyclic peptide crystals was only 0.10 Å for the nonhydrogen atomic positions, and 0.011 Å, 1.0°, and 4.9° for bond lengths, bond angles, and torsional angles, respectively. The parameter set was then further tested by minimizing the high resolution crystal structure of the hydrophobic protein Crambin. The resultant root‐mean‐square deviations for the non‐hydrogen atomic data, in the presence of the crystal lattice, are 0.22 Å, 0.023 Å, 2.0°, and 6.4° for coordinates, bond lengths, bond angles, and torsional angles, respectively.
ORAL: All purpose molecular mechanics simulator and energy minimizer
Authors: Zimmermann Karel
Published: January 2005

A molecular mechanics energy minimizer is presented whose main features are the “floating blocks” and “isles” option, the “a‐NOE” distance inequality constraints and the variable storage first derivative minimization method. The program possibilities are illustrated by examples of molecular docking, energy barrier estimation, modeling of infinite structures, and DNA bending simulations.
A metropolis Monte Carlo method for computing microcanonical statistical rate constants
Authors: Dumont Randall S.
Published: January 2005

A new method of computing microcanonical statistical rate constants is presented. The method utilizes the Metropolis Monte Carlo algorithm in a manner which circumvents some of the numerical inefficiency associated with other Metropolis and “shot‐gun” Monte Carlo based schemes. It is therefore expected to be useful in studies of many degree of freedom systems where numerical efficiency is crucial. Optimization of the method efficiency with respect to its adjustable parameters is examined in detail, both theoretically and in a numerical study of the T‐shaped Ar3 “inversion” process. The energy dependence of the T‐shaped Ar3 inversion rate is studied in a sample application of the method. An application to full three dimensional Ar3 will be presented in a future study.
Splicing I: Using mixed basis sets in ab initio calculations
Authors: Jensen Jan H. , Gordon Mark S.
Published: January 2005

The effect of mixing (or “splicing”) extended and minimal basis sets on molecular properties such as geometries, Mulliken charges, dipoles, and internal rotation barriers was studied for several test molecules. The effect is gauged by comparison with full extended basis set calculations. It is found that splicing improves most properties relative to full minimal basis set calculations, and little accuracy is lost if the splicing is done in a judicious manner.
Conformational energies and rotational barriers in 3‐methyl‐1‐butene and 1‐butene: An ab initio and molecular mechanics study
Authors: Pettersson Ingrid , Gundertofte Klaus
Published: January 2005

The calculated result obtained with MM2(87) for the rotation of the isopropyl group in 3‐methyl‐1‐butene is not in agreement with experimental data. In order to reparametrize the Csp2‐Csp3‐Csp‐Csp3 torsional angle, 3‐methyl‐1‐butene and 1‐butene have been studied by molecular mechanics (MM2(87)) and ab initio (MP2/6‐31G* and MP3/6‐31G*) calculations. The reparametrization of the torsional angle gives calculated results from MM2(87) in agreement with experimental data and ab initio calculations for both 3‐methyl‐1‐butene and 1‐butene. The calculated barriers for the rotation of alkyl groups in alkylbenzenes are improved with these new parameters.
Implementation and use of the method of prudent ascent in conformational analysis using molecular mechanics
Authors: Hooft Rob W. W. , Kanters Jan A. , Kroon Jan
Published: January 2005

In two‐dimensional conformational analysis the current practice is to perform an energy minimization for all possible combinations of two dihedral angles in the molecule, in a fixed order, and apply a certain dihedral angle step‐size. A newly developed method is presented in which the order of the evaluation points on the energy‐surface is not fixed, but is dependent on all previous results in a way which we call “the method of prudent ascent.” In this method the most promising calculation is carried out first, thus minimizing the risk of atomic collisions. In order to be able to take care of the many additional degrees of conformational freedom present in, e.g., carbohydrate molecules, all minimizations are performed using a set of different promising starting conformations on the basis of previous calculations, and only the lowest energy result for each point is saved. An application of the method to conformational analysis of methyl‐cellobiose and the artificial sweetener trichlorogalactosucrose is also presented.
Quantitative comparison of molecular electrostatic potentials for structure‐activity studies
Authors: Richard Ann M.
Published: January 2005

An approach for representing, efficiently calculating and comparing discrete three‐dimensional molecular electrostatic potentials using a quantitative similarity index (MEP‐SI) based on a Carbo‐type formalism is presented. A radial‐type (MACRA) grid representation is described that provides more efficient storage of MEP information than a cubic grid of similar range, appropriate emphasis, and a convenient means for restricting the comparison of MEP functions to a local molecule region. The MACRA based MEP‐SI formalism was used to evaluate the suitability of a variety of approximate methods for efficiently calculating the MEP for use in MEP‐SI comparison of dissimilar molecules. The Mulliken charge method was found inadequate, while the method of potential‐derived charges (PDCs), with additional charges for lone electron pairs included on sulfur, provided an efficient and sufficiently accurate representation of the MEP for this purpose. Convergence of the MEP‐SI with respect to MACRA grid extent and mesh size was demonstrated; the effect of MEP error and different grid point emphasis in the MACRA versus the cubic grid results was investigated, and MEP‐SI results were compared for different forms of the SI equation. The methodology proposed in this study provides an efficient and practical means for comparing MEP functions for two molecules and gives discriminating results for a sample series of molecular analogues consistent with expectations.
Long range nonbonded attractive constants for some charged atoms
Authors: Bartolotti Libero J. , Pedersen Lee G. , Charifson Paul S.
Published: January 2005

Employing the hydrodynamic formulation of time‐dependent Kohn–Sham theory, long range dispersion constants are calculated for some metal ions. We show that these quantities, when used in molecular mechanics calculations or molecular dynamics simulations, lead to excellent results.
Predicting partition coefficients for isomeric diastereoisomers of some tripeptide analogs
Authors: Bodor Nicholas , Huang Ming‐Ju
Published: January 2005

The octanol‐water partition coefficients (Log P) of tripeptide diastereoisomers have been calculated by our recently developed method for predicting Log P from the results of AM1 semiempirical calculations. This method can distinguish different diastereoisomers. The differences arise from variations in molecular conformation, which lead to significant differences in the dipole moment and ovality of the different diastereoisomers.
MSEED: A program for the rapid analytical determination of accessible surface areas and their derivatives
Authors: Perrot G. , Cheng B. , Gibson K.D. , Vila J. , Palmer K.A. , Nayeem A. , Maigret B. , Scheraga H.A.
Published: January 2005

An algorithm for the rapid analytical determination of the accessible surface areas of solute molecules is described. The accessible surface areas as well as the derivatives with respect to the Cartesian coordinates of the atoms are computed by a program called “MSEED,” which is based in part on Connolly's analytical formulas for determining surface area. Comparisons of the CPU time required for MSEED, Connolly's numerical algorithm DOT, and a program for surface area determination (ANA) based on Connolly's analytical algorithm, are presented. MSEED is shown to be as much as 70 times faster than ANA and up to 11 times faster than DOT for several proteins. The greater speed of MSEED is achieved partially because nonproductive computation of the surface areas of internal atoms is avoided. A sample minimization of an energy function, which included a term for hydration, was carried out on MET‐enkephalin using MSEED to compute the solvent‐accessible surface area and its derivatives. The potential employed was ECEPP/2 plus an empirical potential for solvation based on the solvent‐accessible surface area of the peptide. The CPU time required for 150 steps of minimization with the potential that included solvation was approximately twice as great as the CPU time required for 150 steps of minimization with the ECEPP/2 potential only.
Exploring the conformation space of cycloalkanes by linearized embedding
Authors: Crippen Gordon M.
Published: January 2005

Linearized embedding is a variant on the usual distance geometry methods for finding atomic Cartesian coordinates given constraints on interatomic distances. Instead of dealing primarily with the matrix of interatomic distances, linearized embedding concentrates on properties of the metric matrix, the matrix of inner products between pairs of vectors defining local coordinate systems within the molecule. Here, the approach is used to explore the full conformation space allowed to small cyclic alkanes, given the constraint of exact bond lenghts and bond angles. Useful general tools developed along the way are expressions for rotation matrices in any number of dimensions and a generalization of spherical coordinates to any number of dimensions. Analytical results give some novel views of the conformation spaces of cyclopropane, cyclobutane, cyclopentane, and eyclohexane. A combination of numerical and analytical approaches gives the most comprehensive description to date of the cycloheptane conformation space with fixed bond lengths and angles. In this representation, the pseudorotation paths of cyclohexane and cycloheptane are closed curved lines on the surfaces of spheres.
Theoretical calculations of β‐lactam antibiotics. III. AM1, MNDO, and MINDO/3 calculations of hydrolysis of β‐lactam compound (azetidin‐2‐one ring)
Authors: Frau J. , Donoso J. , Muñoz F. , Blanco F. García
Published: January 2005

Semiempirical AM1, MINDO/3, and MNDO methods have been used in the study of the alkaline hydrolysis of β‐lactam antibiotics through a base‐catalyzed, acyl‐cleavage, bimolecular mechanism. In this work, the hydroxyl ion has been chosen as nucleophilic agent and the azetidin‐2‐one ring like a model of β‐lactam antibiotic. The MINDO/3 method does not predict correctly the energies of small rings. This, together with the fact that, like MNDO, it cannot detect the occurrence of hydrogen bonds, gives rise to uncertain estimates of energy barriers. The AM1 method can be considered the most suitable for studying the hydrolysis of β‐lactam compounds.
Conformational analysis of flexible ligands in macromolecular receptor sites
Authors: Leach Andrew R. , Kuntz Irwin D.
Published: January 2005

A computational method for exploring the orientational and conformational space of a flexible ligand within a macromolecular receptor site is presented. The approach uses a variant of the DOCK algorithm [Kuntz et al., J. Mol. Biol., 161, 288 (1982)] to determine orientations of a fragment of the ligand within the site. These positions then form the basis for exploring the conformational space of the rest of the ligand, using a systematic search algorithm. The search incorporates a method by which the ligand conformation can be modified in response to interactions with the receptor. The approach is applied to two test cases, in both of which the crystallographically determined structures are obtained. However, alternative models can also be obtained that differ significantly from those observed experimentally. The ability of a variety of measures of the intermolecular interaction to discriminate among these structures is discussed.
Semiempirical study of compounds with O‐HO intramolecular hydrogen bond
Authors: Ríos Miguel A. , Rodríguez JesúS
Published: January 2005

Application of MNDO, AM1, PM3, MNDO/H, and MNDO/M methods to a set of compounds with intramolecular hydrogen bonds suggested that none of these methods accurately modeled the characteristics of the hydrogen bonds. Since the MNDO/H and MNDO/M methods work well for intermolecular hydrogen bonds, we followed their example and modified MNDO for intramolecular hydrogen bonds by altering the empirical core–core repulsion energy function for all pairs of atoms involved in intramolecular O‐HO bonds. The resulting modified method models the behavior of these bonds quite well, especially as regards their geometry and the barrier to proton transfer. © 1992 by John Wiley & Sons, Inc.
Does CH prefer a C2v rather than a Cs structure?
Authors: Von Ragué Schleyer Paul , De M. Carneiro José Walkimar
Published: January 2005

The closely related Cs (1) and C2v (3) structures of CH have been reinvestigated at many ab initio levels using MP2/6‐31G** and MP2/6‐311 + + G(2df, 2pd) geometries. The largest basis sets employed were 6‐311G(3df, 2p), 6‐311 + + G(3df, 3pd), and the Dunning “correlation consistent” polarized triple‐split valence basis set (cc‐pVTZ). Electron correlation was probed at the MP4 level, but the QCISD method was also used with the largest basis sets. While electron correlation favors 3 over 1 by about 2 kcal/mol, the correlated relative energies with all basis sets employed range from 0.36–1.03 kcal/mol in favor of 1. The best estimate of this difference, 0.86 kcal/mol, is essentially identical with the (scaled) zero‐point energy difference, 0.84 kcal/mol, favoring 3 over 1. These results indicate that 1 and 3 have almost exactly the same energy at 0 K. Our best value for the dissociation energy of CH is 42.0 kcal/mol [QCISD(T)/6‐311 + + G(3df, 3pd)//MP2(fu)/6‐311 + + G(2df, 2pd), corrected to 298 K], which agrees very well with the experimental value. © 1992 by John Wiley & Sons, Inc.
Extended Koopmans' theorem: Approximate ionization energies from MCSCF wave functions
Authors: Morrison Robert C. , Liu Guanghua
Published: January 2005

The extended Koopmans' theorem has been implemented using multiconfigurational self‐consistent field wave functions calculated with the GAMESS, HONDO, and SIRIUS programs. The results of illustrative calculations are presented for the molecules HF, H2O, NH3, CH4, N2, CO, HNC, HCN, C2H2, H2CO, and B2H6. The lowest extended Koopmans' theorem ionization potentials agree well within the experimental values and the ionization potentials representing excited states of the ions show some improvements over the Koopmans' theorem values in most cases. The extended Koopmans' theorem is easily implemented and the time required to calculate the ionization energies is insignificant compared to the time required to calculate the wave function of the un‐ionized molecule. © 1992 by John Wiley & Sons, Inc.
Multicenter point charge model for high‐quality molecular electrostatic potentials from AM1 calculations
Authors: Rauhut Guntram , Clark Timothy
Published: January 2005

The natural atomic orbital/point charge (NAO‐PC) model based upon the AM1 wave function has been developed to calculate molecular electrostatic potentials (MEPs). Up to nine point charges (including the core charge) are used to represent heavy atoms. The positions and magnitudes of the eight charges that represent the atomic electron cloud are calculated from the natural atomic orbitals (NAOs) and their occupations. Each hybrid NAO is represented by two point charges situated at the centroid of each lobe. The positions of the centroids and the magnitudes of the charges were obtained by numerical integration of the Slater‐type hybrids and the results used to set up polynomials and look‐up tables that replace the integration step in the actual MEP calculation. The MEPs calculated using this method are found to be in better agreement with those obtained using RHF/6‐31G* than those obtained from the AM1 wave function using Coulson charges or with MOPAC‐ESP. The MEP calculations are extremely fast and have, for instance, been incorporated into an interactive graphics package. © 1993 John Wiley & Sons, Inc.
Substrate specificity of cytochrome P450cam for L‐ and D‐ norcamphor as studied by molecular dynamics simulations
Authors: Bass Michael B. , Ornstein Rick L.
Published: January 2005

In our earlier molecular dynamics simulations, we found that there was a discrepancy between the predicted and experimental product ratios when norcamphor is hydroxylated by cytochrome P450cam. The experimental results suggest that there is a nearly equimolar ratio between the 5‐ and 6‐hydroxynorcamphor (45% 5‐, 47% 6‐, and 8% 3‐hydroxynorcamphor) [W.M. Atkins and S.J. Sligar, J. Am. Chem. Soc., 109, 3754 (1987)]. Our previous simulations predicted predominately from 68–88% 5‐hydroxynorcamphor [M.B. Bass et al., Prot. Struct. Funct. Genet., 13, 26 (1992); M.B. Bass et al., Proc. Natl. Acad. Sci. U.S.A., submitted]. One possible explanation for this discrepancy is that the simulations were performed using D‐norcamphor while the experiments were conducted with racemic norcamphor. The suggestion that norcamphor is the D‐isomer was based upon the similarity with the native substrate D‐camphor. Indeed, the reported crystallographic structure for norcamphor‐bound P450cam models norcamphor as the D‐isomer. Unfortunately, the two stereomers have never been separated. The simulations presented here model the L‐isomer of norcamphor. Three simulations each of the L‐ and D‐isomers of norcamphor bound to cytochrome P450cam were compared to account for the effects due to substrate orientation and the assignment of random velocities. The results presented here show that the L‐isomer of norcamphor is predicted to give rise to predominately 6‐hydroxynorcamphor, while the D‐isomer gives rise to mainly 5‐hydroxynorcamphor. From this data, we infer that racemic norcamphor will give rise to nonracemic 5‐ and 6‐hydroxynorcamphors after oxidation by cytochrome P450cam. © 1993 John Wiley & Sons, Inc.
Global measure of molecular flexibility and shape fluctuations about conformational minima
Authors: Arteca Gustavo A.
Published: January 2005

A method to characterize conformations adopted by chain and cyclic molecules, and to assess their degree of flexibility toward folding, is developed and applied. The proceudure constructs a function A0 from some simple geometric and topological properties of molecular chains. This function provides a global descriptor of the essential shape features of the molecular fold. The descriptor takes a maximum value of 1 for a completely linear or planar structure and a minimum value of 0 for an entangled or globular backbone. In this sense, the function proposed measures the compactness and degree of folding of a configuration. When one monitors the changes in this function along computer‐simulated molecular dynamics trajectories, it is possible to assess the differential stability of conformations as a function of time, temperature, and other factors. Molecules that are stable over time toward adopting conformations with radically different folds are characterized as rigid. Consequently, the procedure provides also a quantitative measure of rigidity and flexibility toward folding. In other words, the fluctuations of A0 provide a quantitative measure of stability whereas the value of A0 gives a measure of the actual type of instant folding pattern. The description is characteristic of the given conformation and not relative to the initial nuclear geometry for the dynamics. The procedure is illustrated by comparing conformations of hexane and cyclohexane at various temperatures and contrasting the dynamics of hexane and decane, both starting from similar conformational minima. © 1993 John Wiley & Sons, Inc.
Evaluation of one‐electron integrals for arbitrary operators V(r) over Cartesian Gaussians: Application to inverse‐square distance and Yukawa operators
Authors: Jensen James O. , Carrieri Arthur H. , Vlahacos Constantine P. , Zeroka Daniel , Hameka Hendrik F. , Merrow Clifton N.
Published: January 2005

A general procedure is presented for generating one‐electron integrals over any arbitrary potential operator that is a function of radial distance only. The procedure outlines that for a nucleus centered at point C integrals over Cartesian Gaussians can be written as linear combinations of 1‐D integrals. These Cartesian Gaussian functions are expressed in a compact form involving easily computed auxiliary functions. It is well known that integrals over the Coulomb operator can be expressed in terms of Fn(T) integrals, where

By means of a substitution for Fn(T) by other simple functions, algorithms that form integrals over an arbitrary function can be generated. Formation of such integrals is accomplished with minor editing of existing code based on the McMurchie–Davidson formalism. Further, the method is applied using the inverse‐square distance and Yukawa potential operators V(r) over Cartesian Gaussian functions. Thus, the proposed methodology covers a large class of one‐electron integrals necessary for theoretical studies of molecular systems by ab initio calculations. Finally, by virtue of the procedure's recursive nature it provides us with an efficient scheme of computing the proposed class of one‐electron integrals. © 1993 John Wiley & Sons, Inc.
Accuracy of free energies of hydration for organic molecules from 6‐31g*‐derived partial charges
Authors: Carlson Heather A. , Nguyen Toan B. , Orozco Modesto , Jorgensen William L.
Published: January 2005

Absolute free energies of hydration have been computed for 13 diverse organic molecules using partial charges derived from ab initio 6‐31G* wave functions. Both Mulliken charges and charges fit to the electrostatic potential surface (EPS) were considered in conjunction with OPLS Lennard–Jones parameters for the organic molecules and the TIP4P model of water. Monte Carlo simulations with statistical perturbation theory yielded relative free energies of hydration. These were converted to absolute quantities through perturbations to reference molecules for which absolute free energies of hydration had been obtained previously in TIP4P water. The average errors in the computed absolute free energies of hydration are 1.1 kcal/mol for the 6‐31G* EPS charges and 4.0 kcal/mol for the Mulliken charges. For the EPS charges, the largest individual errors are under 2 kcal/mol except for acetamide, in which case the error is 3.7 kcal/mol. The hydrogen bonding between the organic solutes and water has also been characterized. © John Wiley & Sons, Inc.
General atomic and molecular electronic structure system
Authors: Schmidt Michael W. , Baldridge Kim K. , Boatz Jerry A. , Elbert Steven T. , Gordon Mark S. , Jensen Jan H. , Koseki Shiro , Matsunaga Nikita , Nguyen Kiet A. , Su Shujun , Windus Theresa L. , Dupuis Michel , Montgomery John A.
Published: January 2005

A description of theab initioquantum chemistry package GAMESS is presented. Chemical systems containing atoms through radon can be treated with wave functions ranging from the simplest closed‐shell case up to a general MCSCF case, permitting calculations at the necessary level of sophistication. Emphasis is given to novel features of the program. The parallelization strategy used in the RHF, ROHF, UHF, and GVB sections of the program is described, and detailed speecup results are given. Parallel calculations can be run on ordinary workstations as well as dedicated parallel machines. © John Wiley & Sons, Inc.
Hydrating peptides using a sprouting technique
Authors: David Carl W.
Published: January 2005

A scheme for generating water coordinates, whose proton orientations are random, and simultaneously generating side chain coordinates of peptides, preparatory to studying solvation of peptides using molecular dynamics schemes is presented in an X‐PLOR context. Examples from the Integrin and Tropomyosin systems are used to illustrate the procedure. © 1994 by John Wiley & Sons, Inc.
Computational study of the hydrolysis of degradable polysaccharide biomaterials: Substituent effects on the hydrolytic mechanism
Authors: Pratt Lawrence M. , Chu C. C.
Published: January 2005

Hyaluronic acid and its derivatives are absorbable polysaccharides which are used extensively in cosmetics and as biomaterials. Two possible mechanisms of degradation, involving an oxocarbenium ion and the corresponding radical cation, are examined by modeling of the saccharide ring and the effects of various ring substituents on the two possible mechanisms. © 1994 by John Wiley & Sons, Inc.
Monte Carlo simulations on short single‐stranded oligonucleotides. I. Application to RNA trimers
Authors: Ghomi Mahmoud , Victor Jean‐Marc , Henriet Charles
Published: January 2005

Monte Carlo (MC) structural simulation of short RNA sequences has been carried out by random variations of the nucleotide conformational angles (i.e., phosphodiester chain torsional angles and sugar pucker pseudorotational angles). All of the chemical bond lengths and valence angles remained fixed during the structural simulation, except those of the sugar pucker ring. In this article we present the simulated structures of RNA trimers—r(AAA) and r(AAG)—obtained at 11°C and 70°C. The influence of various initial conformations (selected as starting points in the MC simulations) on the equilibrium conformations has been discussed. The simulated conformational angles have been compared with those estimated by nuclear magnetic resonance (NMR) spectroscopy. For both of the oligonucleotides studied here, the most stable structures are helical conformations with stacked bases, at 11°C and 70°C. However, when the starting point is a stretched chain, it is found that r(AAA) adopts a reverse‐stacked structure at low temperature (11°C), in which the A3 base is located between the A1 and A2 bases. Although the energies of these conformations (helical and reverse stacked) are very close to each other, the potential barrier between them is extremely high (close to 30 kcal/mol). This hinders the conformational transition from one structure to the other at a given temperature (and in the course of a same MC simulation). However, it is possible to simulate this structural transition by heating the reverse‐stacked structure up to 500°C and cooling down progressively to 70°C and 11°C: Canonical helical structures have been obtained by this procedure. © 1994 by john Wiley & Sons, Inc.
Optimization of solute cavities and van der Waals parameters in ab initio MST‐SCRF calculations of neutral molecules
Authors: Bachs M. , Luque F. J. , Orozco Modesto
Published: January 2005

The cavity used to represent the solute/water interface in Miertus–Scrocco–Tomasi self‐consistent reaction field (MST‐SCRF) calculations of neutral molecules has been optimized by fitting to experimental data. The study is focused on the refinement of the van der Waals radii of polar and apolar hydrogens and of the van der Waals parameters used to compute the dispersion/repulsion contribution to the total free energy of hydration. When a scaling coefficient of 1.25 is used to build the solute cavity, comparison of 6‐31G*/MST results with experimental data demonstrates that the optimum van der Waals radii for hydrogens are around 1.2 Å (apolar) and 0.9 Å (polar). The optimization of the solute cavity and the refinement of the van der Waals parameters lead to root mean square deviations in the computed free energy of hydration of only 0.9 kcal/mol for the 23 molecules considered in this study. © 1994 by John Wiley & Sons, Inc.
Parametrization of a force field for studying some beta‐lactams
Authors: Fernández Berta , Ríos Miguel A.
Published: January 2005

A molecular mechanics force field for studying some beta‐lactams was developed from ab initio and experimental data. The optimized parameters allowed accurate calculation of the geometries of both the compounds on which the parametrization was based and others on which the validity of the predictions was checked. © 1994 by John Wiley & Sons, Inc.
ICM—A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation
Authors: Abagyan Ruben , Totrov Maxim , Kuznetsov Dmitry
Published: January 2005

An efficient methodology, further referred to as ICM, for versatile modeling operations and global energy optimization on arbitrarily fixed multimolecular systems is described. It is aimed at protein structure prediction, homology modeling, molecular docking, nuclear magnetic resonance (NMR) structure determination, and protein design. The method uses and further develops a previously introduced approach to model biomolecular structures in which bond lengths, bond angles, and torsion angles are considered as independent variables, any subset of them being fixed. Here we simplify and generalize the basic description of the system, introduce the variable dihedral phase angle, and allow arbitrary connections of the molecules and conventional definition of the torsion angles. Algorithms for calculation of energy derivatives with respect to internal variables in the topological tree of the system and for rapid evaluation of accessible surface are presented. Multidimensional variable restraints are proposed to represent the statistical information about the torsion angle distributions in proteins. To incorporate complex energy terms as solvation energy and electrostatics into a structure prediction procedure, a “double‐energy” Monte Carlo minimization procedure in which these terms are omitted during the minimization stage of the random step and included for the comparison with the previous conformation in a Markov chain is proposed and justified. The ICM method is applied successfully to a molecular docking problem. The procedure finds the correct parallel arrangement of two rigid helixes from a leucine zipper domain as the lowest‐energy conformation (0.5 Å root mean square, rms, deviation from the native structure) starting from completely random configuration. Structures with antiparallel helixes or helixes staggered by one helix turn had energies higher by about 7 or 9 kcal/mol, respectively. Soft docking was also attempted. A docking procedure allowing side‐chain flexibility also converged to the parallel configuration starting from the helixes optimized individually. To justdy an internal coordinate approach to the structure prediction as opposed to a Cartesian one, energy hypersurfaces around the native structure of the squash seeds trypsin inhibitor were studied. Torsion angle minimization from the optimal conformation randomly distorted up to the rms deviation of 2.2 Å or angular rms deviation of l0° restored the native conformation in most cases. In contrast, Cartesian coordinate minimization did not reach the minimum from deviations as small as 0.3 Å or 2°. We conclude that the most promising detailed approach to the protein‐folding problem would consist of some coarse global sampling strategy combined with the local energy minimization in the torsion coordinate space. © 1994 by John Wiley & Sons, Inc.
Force field for computation of conformational energies, structures, and vibrational frequencies of aromatic polyesters
Authors: Sun H.
Published: January 2005

A CFF931 all‐atom force field for aromatic polyesters based on ab initio calculations is reported. The force field parameters are derived by fitting to quantum mechanical data which include total energies, first and second derivatives of the total energies, and electrostatic potentials. The valence parameters and the ab initio electrostatic potential (ESP) derived charges are then scaled to correct the systematic errors originating from the truncation of the basis functions and the neglect of electron correlation in the HF/6‐31G* calculations. Based on the force field, molecular mechanics calculations are performed for homologues of poly(p‐hydroxybenzoic acid) (PHBA) and poly(ethylene terephthalate) (PET). The force field results are compared with available experimental data and the ab initio results. © 1994 by John Wiley & Sons, Inc.
Hybrid Monte Carlo: An efficient algorithm for condensed matter simulation
Authors: Clamp M. E. , Baker P. G. , Stirling C. J. , Brass A.
Published: January 2005

A detailed comparison has been made of the performance of molecular dynamics and hybrid Monte Carlo simulation algorithms for calculating thermodynamic properties of 2D Lennard‐Jonesium. The hybrid Monte Carlo simulation required an order of magnitude fewer steps than the molecular dynamics simulation to calculate reproducible values of the specific heat. The ergodicity of the two algorithms was compared via the use of intermediate scattering functions. For classical systems the intermediate scattering functions should be real; however, a simple analysis demonstrates that this function will have a significant imaginary component when ergodicity breaks down. For q vectors near the zone boundary, the scattering functions are real for both algorithms. However, for q vectors near the zone center (i.e., harmonic, weakly coupled modes), the scattering function calculated via molecular dynamics had a significantly larger imaginary component than that calculated using hybrid Monte Carlo. Therefore, the hybrid Monte Carlo algorithm is more ergodic and samples phase space more efficiently than molecular dynamics for simulations of 2D Lennard‐Jonesium. © 1994 by John Wiley & Sons, Inc.
Explicitly correlated Gaussian functions with r factors for calculations of the ground state of the helium atom
Authors: Zhang Zhenghong , Adamowicz Ludwik
Published: January 2005

Explicitly correlated Gaussian functions with r exp( − βr) factors have been used in variational calculations of the ground state of the helium atom. Additional correlation factors in the form of even powers of rij were introduced to the Gaussian functions with exponential correlation components by differentiating these functions with respect to the correlation exponent β. The algorithm of this method and its computational implementation is described. A number of calculations were performed for the ground state of helium atom to test the performance of the basis sets comparising different numbers of the Gaussians with the exp( − βr) and r exp( − βr) correlation factors. The numerical results indicate that including functions with r factors does not lead to improved results, contrary to what was anticipated initially. © 1994 by John Wiley & Sons, Inc.
GEPOL: An improved description of molecular surfaces. III. A new algorithm for the computation of a solvent‐excluding surface
Authors: Pascual‐ahuir J. L. , Silla E. , Tuñon I.
Published: January 2005

To understand and calculate the interactions of a solute with a solvent, a good method of computing the molecular surface is needed. Three kinds of surfaces may be used: the van der Waals Surface, the Accessible Surface, and the Molecular Surface. The latter is redefined in this article as the Solvent‐Excluding Surface. The new algorithm for computing the Solvent‐Excluding Surface included in the GEPOL93 program is described. GEPOL93 follows the same concept as former versions of GEPOL but with a full new algorithm. Thus, it computes the Solvent‐Excluding Surface by filling the spaces not accessible to the solvent with a set of new spheres. The computation is controlled by three parameters: the number of triangles per sphere, controlled by NDIV; the maximum overlap among the new spheres (OFAC); and the size of the smallest sphere that can be created (RMIN). The changes introduced for the computation of the ESURF make GEPOL93 not just a new version but a new program. An estimation is made of the error in the area and volume obtained in the function of the parameters. © 1994 by John Wiley & Sons, Inc.
Is the stereomutation of methane possible?
Authors: Pepper Melanie J. M. , Shavitt Isaiah , Schleyer Paul Von Ragué , Glukhovtsev Mikhail N. , Janoschek Rudolf , Quack Martin
Published: January 2005

Large basis set ab initio calculations at correlated levels, including MP2, single reference, as well as multireference configuration interaction, carried out on the methane potential energy surface, have located and characterized a transition structure for stereomutation (one imaginary frequency). This structure is best described as a pyramidal complex between singlet methylene and a side‐on hydrogen molecule with Cs symmetry. At the single reference CI level, it lies 105 kcal/mol above the methane Td‐ground state but is stable relative to dissociation into CH2(1A1) and H2 by 13 kcal/mol at 0 K (with harmonic zero point energy (ZPE) corrections for all structures). Dissociation of the transition state into triplet methylene and hydrogen also is endothermic (by 4 kcal/mol), but single bond rupture to give CH and H. is 3 kcal/mol exothermic. Thus, it does not appear likely that methane can undergo stereomutation classically beneath the dissociation limit. Confirming earlier conclusions, side‐on insertion of 1A1 CH2 into H2 in a perpendicular geometry occurs without activation energy. Planar (D4h) methane (130.5 kcal/mol) has four imaginary frequencies. Two of these are degenerate and lead to equivalent planar C2v structures with one three‐center, two‐electron bond and two two‐electron bonds and two imaginary frequencies. The remaining imaginary frequencies of the D4h form lead to tetrahedral (Td) and pyramidal (C4v) methane. The latter has three negative eigenvalues in the force‐constant matrix; one of these leads to the Td global minimum and the other to the Cs (parallel) stereomutation transition structure. Multireference CI calculations with a large atomic natural orbitals basis set produce similar results, with the electronic energy of the Cs stereomutation transition state 0.7 ± 0.5 kcal/mol higher than that of CH + H. dissociation products, and a ZPE‐corrected energy which is 5 ± 1 kcal/mol higher. Also considered are photochemical pathways for stereomutation and the possible effects of nuclear spin, inversion tunneling, and the parity‐violating weak nuclear interaction on the possibility of an experimental detection of stereomutation in methane. © 1995 by John Wiley & Sons, Inc.
An efficient simulation technique for electrostatic free energies with applications to azurin
Authors: Svensson Bo , Jönsson Bo
Published: January 2005

We present an efficient technique for Monte Carlo simulation of electrostatic free energy changes in biomolecular systems. It is a development of a recent method for the study of the influence of electrostatic interactions on the ion binding properties and redox potentials of biomolecules. The electrolyte solution is described by the primitive model, in which ions are treated as hard charged spheres and the solvent is replaced by a structureless continuum. The protein is kept fixed in the center of a spherical simulation cell, and the dielectric constant has the solvent value throughout the cell. By a multiparticle perturbation approach, it is possible to obtain a number of free energy changes within one simulation only. The usefulness of the method is illustrated with a study of the copper binding electron‐transport protein azurin (from Alcaligenes denitrificans). The change in acidity of the histidine residues upon changing the redox state of the copper ion is calculated. The theoretical predictions agree well with available experiments. © 1995 by John Wiley & Sons, Inc.
Improved methods for semiempirical solvation models
Authors: Liotard Daniel A. , Hawkins Gregory D. , Lynch Gillian C. , Cramer Christopher J. , Truhlar Donald G.
Published: January 2005

We present improved algorithms for the SMx (x = 1, 1a, 2, 3) solvation models presented previously [see the overview in C. J. Cramer and D. G. Truhlar, J. Comp.‐Aided Mol. Design, 6, 629 (1992)]. These models estimate the free energy of solvation by augmenting a semiempirical Hartree‐Fock calculation on the solute with the generalized Born (GB) model for electric polarization of the solvent and a surface tension term based on solvent‐accessible surface area. This article presents three improvements in the algorithms used to carry out such calculations, namely (1) an analytical accessible surface area algorithm, (2) a more efficient radial integration scheme for the dielectric screening computation in the GB model, and (3) a damping algorithm for updating the GB contribution to the Fock update during the iterations to achieve a self‐consistent field. Improvements (1) and (2) decrease the computer time, and improvement (3) leads to more stable convergence. Improvement (2) removes a small systematic numerical error that was explicitly absorbed into the parameterization in the SMx models. Therefore, we have adjusted the parameters for one of the previous models to yield essentially identical performance as was obtained originally while simultaneously taking advantage of improvement (2). The resulting model is called SM2.1. The fact that we obtain similar results after removing the systematic quadrature bias attests to the robustness of the original parameterization. © 1995 by John Wiley & Sons, Inc.
The relaxation of molecular crystal structures using a distributed multipole electrostatic model
Authors: Willock D. J. , Price S. L. , Leslie M. , Catlow C. R. A.
Published: January 2005

We describe a method for minimizing the lattice energy of molecular crystal structures, using a realistic anisotropic atom–atom model for the intermolecular forces. Molecules are assumed to be rigid, and the structure is described by the center of mass positions and orientational parameters for each molecule in the unit cell, as well as external strain parameters used to optimize the cell geometry. The resulting program uses a distributed multipole description of the electrostatic forces, which consists of sets of atomic multipoles (charge, dipole, quadrupole, etc.) to represent the lone pair, π electron density, and other nonspherical features in the atomic charge distribution. Such ab initio based, electrostatic models are essential for describing the orientation dependence of the intermolecular forces, including hydrogen bonding, between polar molecules. Studies on a range of organic crystals containing hydrogen bonds are used to illustrate the use of this new crystal structure relaxation program, DMAREL, and show that it provides a promising new approach to studying the crystal packing of polar molecules. © 1995 by John Wiley & Sons, Inc.
Energetics of Zn2+ binding to a series of biologically relevant ligands: A molecular mechanics investigation grounded on ab initio self‐consistent field supermolecular computations
Authors: Gresh Nohad
Published: January 2005

Detailed investigations are performed of the binding energetics of Zn2+ to a series of neutral and anionic ligands making up the sidechains of amino acid residues of proteins, as well as ligands which can be involved in Zn2+ binding during enzymatic activation: imidazole, formamide, methanethiol, methanethiolate, methoxy, and hydroxy. The computations are performed using the SIBFA molecular mechanics procedure (SMM), which expresses the interaction energy under the form of four separate contributions related to the corresponding ab initio supermolecular ones: electrostatic, short‐range repulsion, polarization, and charge transfer. Recent refinements to this procedure are first exposed. To test the reliability of this procedure in large‐scale simulations of inhibitor binding to metalloenzyme cavities, we undertake systematic comparisons of the SMM results with those of recent large basis set ab initio self‐consistent field (SCF) supermolecule computations, in which a decomposition of the total ΔE into its four corresponding components is done (N. Gresh, W. Stevens, and M. Krauss, J. Comp. Chem., 16, 843, 1995). For each complex, the evolution of each individual SMM energy component as a function of radial and in‐ and out‐of‐plane angular variations of the Zn2+ position reproduces with good accuracy the behavior of the corresponding SCF term. Computations performed subsequently on di‐ and oligoligated complexes of Zn2+ show that the SIBFA molecular mechanics (SMM) functionals, Epol and Ect, closely account for the nonadditive behaviors of the corresponding second‐order energy contributions determined from the ab initio SCF calculations on these complexes and their nonlinear dependence on the number of ligands. Thus, the total intermolecular interaction energies computed with this procedure reproduce, with good accuracy, the corresponding SCF ones without the need for additional, extraneous terms in the intermolecular potential of polyligated complexes of divalent cations. © 1995 by John Wiley & Sons, Inc.