摘要:

AbstractWe describe the development of Metropolis Monte Carlo algorithms for a general network of multiple instruction multiple data (MIMD) parallel processors. The implementation of farm, event, and systolic parallel algorithms on transputer‐based computers is detailed and their relative performance discussed. Although the emphasis is on methodology, the application of such parallel algorithms will be important for addressing computational problems such as the determination of free energy differences in complex biologically important molecular systems. © 1993 John Wiley&Sons, I

ISSN:0192-8651    

DOI:10.1002/jcc.540140202

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe first ionization potential of an organic molecule containing electrons in nonbonding or π‐type molecular orbitals can rapidly be calculated using parameters describing physical and chemical effects. These parameters include effective polarizability, resonance stabilization of a cation, π‐ and σ‐charges, and electronegativity and are directly calculated from the structure of the compound. Correlation analyses with the first ionization potentials were carried out on various data sets classified into five groups to cover a wide range of organic molecules. The equations thus obtained were integrated into a system that automatically calculates the ionization potential of an organic compound from a connection table as obtained by a graphic input program. © 1993 John Wiley&

ISSN:0192-8651    

DOI:10.1002/jcc.540140203

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractTwo new types of real (i.e., noninteger) local vertex invariants (LOVIs), denoted byciandc′iand called distance‐enhanced exponential connectivities, are defined via eqs. (1)–(3) and (1′)–(3′), respectively. Only the case when the exponentzequals 1 in eqs. (3) and (3′) is discussed in detail. Both these LOVIs span the range from 0–1, but their dependence upon topology is fairly different, as seen from Table II, whereciandc′ivalues for all heptane and octane isomers are displayed. From these LOVIs, by simple summation over all graph vertices two new topological indexes (TIs), denoted byXCandXC′, respectively, are obtained. Their intermolecular ordering of all alkanes with four to nine carbon atoms is discussed. On their basis, correlations with boiling points and critical pressures of alkanes are presented. © 1993

ISSN:0192-8651    

DOI:10.1002/jcc.540140204

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractDifferent microscopic and semimicroscopic approaches for calculations of electrostatic energies in macromolecules are examined. This includes the Protein Dipoles Langevin Dipoles (PDLD) method, the semimicroscopic PDLD (PDLD/S) method, and a free energy perturbation (FEP) method. The incorporation of these approaches in the POLARIS and ENZYMIX modules of the MOLARIS package is described in detail. The PDLD electrostatic calculations are augmented by estimates of the relevant hydrophobic and steric contributions, as well as the effects of the ionic strength and external pH. Determination of the hydrophobic energy involves an approach that considers the modification of the effective surface area of the solute by local field effects. The steric contributions are analyzed in terms of the corresponding reorganization energies. Ionic strength effects are studied by modeling the ionic environment around the given system using a grid of residual charges and evaluating the relevant interaction using Coulomb's law with the dielectric constant of water. The performance of the FEP calculations is significantly enhanced by using special boundary conditions and evaluating the long‐range electrostatic contributions using the Local Reaction Field (LRF) model. A diverse set of electrostatic effects are examined, including the solvation energies of charges in proteins and solutions, energetics of ion pairs in proteins and solutions, interaction between surface charges in proteins, and effect of ionic strength on such interactions, as well as electrostatic contributions to binding and catalysis in solvated proteins. Encouraging results are obtained by the microscopic and semimicroscopic approaches and the problems associated with some macroscopic models are illustrated. The PDLD and PDLD/S methods appear to be much faster than the FEP approach and still give reasonable results. In particular, the speed and simplicity of the PDLD/S method make it an effective strategy for calculations of electrostatic free energies in interactive docking studies. Nevertheless, comparing the results of the three approaches can provide a useful estimate of the accuracy of the calculated energies. © 1993 John Wiley&Sons, I

ISSN:0192-8651    

DOI:10.1002/jcc.540140205

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe potential energy surface of HCP converting to HPC in its ground electronic state has been investigated withab initiomethods 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

ISSN:0192-8651    

DOI:10.1002/jcc.540140206

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractIntermolecular potential functions have been developed for use in computer simulations of substituted benzenes. Previously reported optimized potentials for liquid simulations (OPLS) for benzene and organic functional groups were merged and tested by computing free energies of hydration for toluene,p‐xylene, phenol, anisole, benzonitrile,p‐cresol, hydroquinone, andp‐dicyanobenzene. The calculations featured Monte Carlo simulations at 25°C and 1 atm with statistical perturbation theory. The average difference between the computed results and experimental data for the absolute free energies of hydration is 0.5 kcal/mol. The AM1‐SM2 method is also found to perform well in predicting the free energies of hydration for the substituted benzenes. In addition, the Monte Carlo simulations provided details on the hydration of the substituted benzenes, in particular for the solute–water hydrogen bonding. © 1993 John Wile

ISSN:0192-8651    

DOI:10.1002/jcc.540140207

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractIntermolecular potential functions have been developed for use in computer simulations of substituted benzenes. Previously reported optimized potentials for liquid simulations (OPLS) for benzene and organic functional groups were merged and tested in Monte Carlo statistical mechanics simulations for the pure liquids of toluene,m‐cresol, anisole, aniline, and benzonitrile at 25°C at 1 atm. The merged potential functions yielded acceptable thermodynamic results for the liquids except in the case of aniline, for which the error in the heat of vaporization was 12%. This was remedied by enhancing the polarity of the model to be more consistent with the observed dipole moment of aniline. Overall, the average errors in computed heats of vaporization and densities were then 2 and 1%, respectively. The structures of the liquids were characterized through energy and radial distribution functions. Form‐cresol and aniline, the molecules participate in averages of 1.6 and 1.4 hydrogen bonds, respectively. Condensed phase effects on the torsional energies for anisole,m‐cresol, and aniline were found to be small;m‐cresol has a slightly enhanced tendency to be nonplanar in the liquid than in the gas phase, while anisole shows the opposite pattern. © 1993 John Wiley&

ISSN:0192-8651    

DOI:10.1002/jcc.540140208

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractA series ofab initioelectronic structure calculations have been performed on the (H3Si)2O molecule using a range of basis sets. The accuracy of these calculations was evaluated by comparison with several experimental measurements. These calculations support earlier results indicating that polarization functions on the bridging oxygen atom are usually required to obtain a bent geometry for the Si‐O‐Si linkage in disiloxane. It was found thatab initiocalculations utilizing effective core potentials and a double‐ζ valence description augmented with polarization functions (CEP‐31G*) provide results comparable in quality to those obtained using the all‐electron 6‐31G* basis set. To demonstrate the general utility of these effective core potential basis sets for theoretical studies of molecular silicates, calculations were performed on the (HO)3SiOSi(OH)3molecule. The results obtained are in excellent agreement with previous experimental andab initiocalculations using all‐electron basis sets. © 1993 John

ISSN:0192-8651    

DOI:10.1002/jcc.540140209

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractIn this article, we describe the program MORMIN, which can simultaneously minimize the mechanical energy of a given macromolecular structure, together with a weighted quadratic penalty function of the difference between the observed and computed nuclear Overhauser effect (nOe) peaks. The gradient of the nOe penalty function relatively to the proton coordinates is computed from an exact closed formula of a matrix exponential derivative. To cut CPU time, the molecular system is partitioned into nonoverlapping subsets containing the protons involved in the observed peaks. The algorithm is no longer exact, but if a 1% relative error is accepted it can be run, on a scalar computer, in about the same CPU time as needed for the calculation of the mechanical energy. We have successfully run the program in more than 1000 situations, including cases where the hybrid method failed because of the occurrence of negative eigenvalues. In some cases, the optimization of the Cartesian coordinates could be successfully extended to individual atomic diffusion times. © 1993 John Wiley&Sons, Inc

ISSN:0192-8651    

DOI:10.1002/jcc.540140210

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe affinity of a ligand for a receptor is usually expressed in terms of the dissociation constant (Ki) of the drug‐receptor complex, conveniently measured by the inhibition of radioligand binding. However, a ligand can be an antagonist, a partial agonist, or a full agonist, a property largely independent of its receptor affinity. This property can be quantitated as intrinsic activity (1A), which can range from 0 for a full antagonist to 1 for a full agonist. Although quantitative structure–activity relationship (QSAR) methods have been applied to the prediction of receptor affinity with considerable success, the prediction of IA, even qualitatively, has rarely been attempted. Because most traditional QSAR methods are limited to congeneric series, and there are often major structural differences between agonists and antagonists, this lack of success in predicting IA is understandable. To overcome this limitation, we used the method of comparative molecular field analysis (CoMFA), which, unlike traditional Hansch analysis, permits the inclusion of structurally dissimilar compounds in a single QSAR model. A structurally diverse set of 5‐hydroxytryptamine1A(5‐HT1A) receptor ligands, with literature IA data (determined by the inhibition of 5‐HT sensitive forskolin‐stimulated adenylate cyclase), was used to develop a 3‐D QSAR model correlating intrinsic activity with molecular structure properties of 5HT1Areceptor ligands. This CoMFA model had a crossvalidatedr2of 0.481, five components and final conventionalr2of 0.943. The receptor model suggests that agonist and antagonist ligands can share parts of a common binding site on the receptor, with a primary agonist binding region that is also occupied by antagonists and a secondary binding site accommodating the excess bulk present in the sidechains of many antagonists and partial agonists. The CoMFA steric field graph clearly shows that agonists tend to be “flatter” (more coplanar) than antagonists, consistent with the difference between the 5‐HT1Aagonist and antagonist pharmacophores proposed by Hibert and coworkers. The CoMFA electrostatic field graph suggests that, in the region surrounding the essential protonated aliphatic amino group, the positive molecular electrostatic potential may be weaker in antagonists as compared to agonists. Together, the steric and electrostatic maps suggest that in the secondary binding site region increased hydrophobic binding may enhance antagonist activity. These results demonstrate that CoMFA is capable of generating a statistically crossvalidated 3‐D QSAR model that can successfully distinguish between agonist and antagonist 5‐HT1Aligands. To the best of our knowledge, this is the first time this or any other QSAR method has been successfully applied to the correlation of structure with IA rather than potency or affinity. The analysis has suggested various structural features associated with agonist and antagonist behaviors of 5‐HT1Aligands and thus should assist in the future design of drugs that act via 5‐HT1Areceptors.

ISSN:0192-8651    

DOI:10.1002/jcc.540140211

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY