摘要:

AbstractThe free energy gradient or Hessian of a molecule interacting with a liquid represented by a dielectric continuum is derived in the self‐consistent reaction field formalism. Anellipsoidal approximationof the cavity is proposed with an algorithm to automatically define the ellipsoid from the nuclear coordinates of the atoms. With this approximation, geometry optimization of the solvated molecule becomes very fast. This method has been implemented in some standardab initioor semiempirical computational codes. As a first test of the method, full geometry optimization of formamide in a high dielectric constant medium reveals that the CPU time needed for one optimization cycle is less than 3% longer for a solvated species than for the corresponding free molecul

ISSN:0192-8651    

DOI:10.1002/jcc.540130602

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractSemiempirical 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‐

ISSN:0192-8651    

DOI:10.1002/jcc.540130603

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractA hybrid conformational search algorithm (DMC) is described that combines a modified form of molecular dynamics with Metropolis Monte Carlo sampling, using the COSMIC(90) force field. Trial configurations are generated by short bursts of high‐temperature dynamics in which the initial kinetic energy is focused into single bond rotations or alternatively into “corner‐flapping” motions in ring systems. Constant temperature and simulated annealing search protocols have been applied to the conformational analysis of several model hydrocarbons (cyclopentane, cyclohexane, cycloheptane, cyclooctane, cycloheptadecane, decane, and tetradecane), and the performance compared with conventional molecular dynamics and Monte Carlo sampling methods. Optimum Metropolis sampling temperatures have been determined and range from 1000–2000 K for acyclic molecules to 3000 K for cyclic systems. Simulated annealing runs are most successful at locating the global minimum when cooling slowing from these optimum tem

ISSN:0192-8651    

DOI:10.1002/jcc.540130604

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractAb initioand 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 withab initiotheory 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−1relative to the active site model and 19.6 kcal mol−1relative to the most stable point on the calculate

ISSN:0192-8651    

DOI:10.1002/jcc.540130605

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe geometry of acryloyl fluoride was optimized completely at the RHF/6‐31G* level of theory at 10 points on the theoretical potential energy curve for internal rotation. The energies obtained were used to determine a six term cosine expansion of the torsional potential energy function. This function was then refined using the experimental torsional transition frequencies in thes‐transands‐ciswells in conjunction with the geometrical parameters optimized at the RHF/6‐31G* level. The effective potential function obtained is compared with previous results. The necessity of accounting for relaxation of the geometry upon internal rotation is stressed. © 1992 by John Wiley&S

ISSN:0192-8651    

DOI:10.1002/jcc.540130606

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractAnab initiostudy of 3‐chloro‐, 3‐hydroxy‐, 3‐mercapto‐, and 3‐amino‐propanenitrile and 4‐chloro‐bu‐ tanenitrile was carried out at several levels of theory. The calculated stabilities and geometrical trends are interpreted in terms of the effects of intramolecular hydrogen bonds and anomeric interactions, and compared with availa

ISSN:0192-8651    

DOI:10.1002/jcc.540130607

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractA 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.

ISSN:0192-8651    

DOI:10.1002/jcc.540130608

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractA large data base of 6‐31G*, MNDO, AM1, and PM3 electrostatic potential (ESP) derived point charges of amino acids and monosaccharides is analyzed. We find that MNDO correlates well with 6‐31G* ESP derived point charges, while AM1 and PM3 do so quite poorly. Furthermore, scaling MNDO ESP derived point charges enhances the ability of MNDO to reproduce 6‐31G* results. We used our data base to attempt to derive a 6‐31G* transferable charge model at an atom‐by‐atom level. We find that it is simple to derive a transferable model for monosaccharides, but for the amino acids statistical difficulties make this a less attractive approach. The transferable charge model for the monosaccharides is slightly better than MNDO, but scaled MNDO charges perform significantly better than the transferable model. We also carried out a QMD simulation on the alanine dipeptide to assess the fluctuations that would be expected in atomic point charges during the course of an MD simulation. Relatively large charge fluctuations are observed and their impact on molecular simulation is addressed. © 1992 by John Wil

ISSN:0192-8651    

DOI:10.1002/jcc.540130609

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractFinite‐difference Poisson–Boltzmann (FDPB) methods allow a fast and accurate calculations of the reaction field (charge–solvent) energies for molecular systems. Unfortunately, the energy in the FDPB calculations includes the self‐energies and the finite‐difference approximation to the Coulombic energies as well as the reaction field energy. A second finite‐difference calculation, in a uniform dielectric, is therefore necesssary to eliminate these contributions. In this article we describe a rapid and accurate method to calculate the self energy and finite‐difference Coulombic energies in a uniform dielectric thus eliminating the need for a second finite‐difference calculation. The computational savings for this method range from a factor of 4 for a typical protein to a factor of 103for small molecules. © 1992 by John

ISSN:0192-8651    

DOI:10.1002/jcc.540130610

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY

摘要:

AbstractQuantum mechanical (ab initioand semiempirical) and force field calculations are reported for representative torsion potentials in several tetrahydropyran derivatives. The overall agreement between the various methods is quite good except that the AMBER torsion profiles are sensitive to the choice of atomic point charges. Using electrostatic potential (ESP) derived atomic point charges determined with the STO‐3G basis set we find that AMBER is able to match the best quantum mechanical results quite well. However, when the point charges are derived using the 6‐31G* basis set we find that scaling the intramolecular electrostatic nonbond interactions is necessary. AM1 does not work very well for these compounds when compared to theab initiomethods and, therefore, should only be used in cases whenab initiocalculations would be prohibitive. Based upon our results we feel that any force field that makes use of 6‐31G* ESP derived atomic point charges will need to scale intramolecular interactions. Implications of scaling intramolecular interactions to the development of force fields based on 6‐31G* ESP derived atomic point charges are discussed. © 1992 by John Wiley&S

ISSN:0192-8651    

DOI:10.1002/jcc.540130611

出版商:John Wiley&Sons, Inc.    

年代:1992

数据来源: WILEY