ISSN:0021-2148    

DOI:10.1002/ijch.198600020

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

ISSN:0021-2148    

DOI:10.1002/ijch.198600021

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractAn experimental parallel computer system which is expected to achieve supercomputing performance is described. This system allows the execution of single large jobs on multiple processors. The system hardwares and softwares will be briefly described. The validity of this approach to performing large scale simulations of biological systems is verified by analyzing the performance results of a variety of application programs. Among the applications to be discussed are programs in quantum chemistry, statistical mechanics and fluid dynamics. Specific examples of large biological systems which have been studied shall also be discussed.

ISSN:0021-2148    

DOI:10.1002/ijch.198600022

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractConformational energy calculations provide an understanding as to how interatomic interactions lead to the three‐dimensional structures of polypeptides and proteins, and how these molecules interact with other molecules. Illustrative results of such calculations pertain to model systems (α‐helices and β‐sheets, and interactions between them), to various open‐chain and cyclic peptides, to fibrous proteins, to globular proteins, and to enzyme‐substrate complexes. In most cases, the validity of the computations is established by experimental tests of the predicted

ISSN:0021-2148    

DOI:10.1002/ijch.198600023

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractRecently developed integral equation methods for the evaluation of intermolecular and intramolecular interactions in a polar solvent medium are discussed and representative applications are presented. Examples include solvent modification of interionic interactions between atomic or molecular ions in water and liquid environment induced shifts in conformational equilibria for both non‐polar and polar flexible molecules in water. Emphasis is placed on the features of these phenomena which can be traced specifically to the molecularity of the solvent and hence cannot be adequately reproduced by a simple continuum dielectric solvent representatio

ISSN:0021-2148    

DOI:10.1002/ijch.198600024

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractA series of liquid state Monte Carlo computer simulations on the N‐methyl acetamide in water (NMA molecule) are described, considering both thecisandtransisomeric forms of NMA. Two independent sets of calculations were performed, one set based on the potential functions developed by Clementi and co‐workers (CPF) used in conjunction with the Matsuoka et al. (MCY) water‐water potential, and the other set using the OPLS potential of Jorgensen and coworkers for solute‐water interactions and the TIP4P potential for the water‐water interactions. The relative hydration energies of thecisandtransisomers of NMA and the transfer energies of NMA from free space to water are discussed with respect to the convergence level of the simulations and the sensitivity of results to the choice of the intermolecular potential functions. The structural chemistry of the aqueous hydration for NMA is developed from the simulation result based on Proximity Analysis. The sensitivity of the structural and energetic indices of analysis to choice of potential is described. Preliminary results of the calculation of the hydration contribution to the free energy are also

ISSN:0021-2148    

DOI:10.1002/ijch.198600025

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractThe use of molecular dynamics simulations to study the internal motions and structural flexibility of proteins and nucleic acids has received a great deal of attention in recent years. The attraction of the method is, in part, its potential for studying detailed properties of biological macromolecules that are only indirectly accessible to experiment. Equally important is the use of the method to provide a more fundamental understanding of the molecular information contained in various kinds of experiments on these complex systems. In this paper we review recent work in our laboratory concerned with the use of computer simulations for the interpretation of experimental probes of molecular structure and dynamics of proteins and nucleic acids. The interplay between computer simulations and three experimental techniques are emphasized: (1) nuclear magnetic resonance relaxation spectroscopy; (2) refinement of macromolecular X‐ray structures; and (3) vibrational spectroscop

ISSN:0021-2148    

DOI:10.1002/ijch.198600026

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractIn recent years a procedure has been developed by which the three‐dimensional (3D) structure of biomolecules can be derived from 2D NMR data. This procedure combines model building with restrained energy minimization (EM) and molecular dynamics (MD) techniques. Distance information from NOE's is incorporated in the form of an upper limit distance restraining term that is added to the interatomic potential function.Here, two improvements of the refinement procedure are introduced. First, the information that is contained in empty parts of 2D‐NOE spectra is transformed into, so‐called, non‐NOE's which are modelled by adding a lower limit distance restraining term to the potential function for each non‐NOE proton pair. Secondly, the information that is contained in the occurrence of large J‐coupling constants for specific dihedrals is modelled by adding a sinusoidal dihedral angle restraining term to the potential function for each dihedral angle with a large J‐value.The improved refinement procedure is tested by application of thelacrepressor headpiece. Both the inclusion of non‐NOE data and the inclusion of J‐coupling information markedly improve the result of the restrained MD refinement of headpiece. In the refinement procedure MD simulation is used for searching configuration space. Energy barriers which are too high to be crossed by MD are surmounted by manually changing the model structures on a picture system. The resulting close non‐bonded contacts are relaxed by EM.The final structure of headpiece satisfies essentially all 169 NOE and 9529 non‐NOE distance constraints as well as the 6Cα– Cβdihedral angle values corresponding to the m

ISSN:0021-2148    

DOI:10.1002/ijch.198600027

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractWe present the results of molecular dynamics simulations on base paired deoxyribonucleotides dA10·dT10, d(GCGCGCGCGC)2d(ATATATATAT)2d(CGCGA)·d(TCACG) (AC mismatch) and d(CGAGA)·d(TCGCG) (GA mismatch). The average structural properties — helix parameters, H‐bond parameters, sugar puckers, torsional angles, root mean square atomic fluctuations — are compared to those found in earlier studies on the sequence d(CGCGA)·d(TCGCG).1The properties of the decamer helices remain B DNA like throughout the simulation, confirming our inference1that a model which treats solvent/counterions in a simple fashion (full charge on phosphates, but use of large hydrated counterions and a distance dependent dielectric constant) is a reasonable “first order” model to simulate the properties of DNA helices over periods of at least 100 psec. There are a number of sequence dependent effects observed in the three decanucleotides studied here, among them differences in H‐bond properties, sugar pucker and helix repeat/base tilts. In d(GCGCGCGCGC)2and d(ATATATATAT)2the H‐bonds all stay near the classic Watson‐Crick distance and the base tilts and twists are small (10–20°). On the other hand, in dA10·dT10there are much larger deviations of H‐bonding from classic Watson‐Crick and H‐bond exchange during the simulation. There are many more examples of sugar repuckering in the AT decamers, and the relative frequency of such repuckering is qualitatively consistent with what one would expect based on molecular mechanics studies. A comparison of the torsional angles, sugar puckers, helical parameters, root mean square atom amplitudes and hydrogen bond parameters of the sequence d(CGCGA)·d(TCGCG) with the two mismatched analogues demonstrates that the effect of the poorer hydrogen bonding at the central base pair is transmitted throughout the sequence, leading to significantly greater root mean square fluctuations in all dihedral angles, significantly higher % of non‐“standard C2′ endo” sugar puckers, generally longer H‐bond distances, with greater % of “long” H bonds during the simulation, larger RMS amplitude of atomic fluctuations and greater helix twist and tilt of the base pairs. The average helix repeat is 9.0 for the AC mismatch, and 10.1 for the GA mismat

ISSN:0021-2148    

DOI:10.1002/ijch.198600028

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY

摘要:

AbstractIn this paper, we report on studies of ligand binding to the enzyme dihydrofolate reductase (DHFR). Energy minimizations of four complexes of DHFR with the inhibitor trimethoprim, an antibiotic, and the cofactor NADPH have been carried out in order to investigate the energetics responsible for the 100,000‐fold increase in binding affinity of trimethoprim toE. coliDHFR compared with chicken liver DHFR. Several factors suggested to be responsible for the enhanced binding in bacterial DHFR's were investigated in terms of intermolecular and intramolecular energetics. The strain energies of trimethoprim in the four complexes were calculated and found to be about 6 kcal mol−1in all complexes of the two species. In the binary complex of chicken liver DHFR, where the largest variation was observed, 2 kcal mol−1higher than in the other complexes, it was found that this increase was compensated for by the slightly more favorable intermolecular interaction of the trimethoxyphenyl moiety with the protein.Comparison of the minimized binary and ternary complexes ofE. coliallowed us to investigate the cooperativity in the binding of trimethoprim and NADPH in the bacterial enzyme in terms of the underlying intermolecular forces. This cooperativity was found to be due to a direct trimethoprim ‐ NADPH interaction in theE. colienzyme rather than enhanced protein‐inhibitor interactions induced upon binding of the cofactor. These interactions are not as favorable in the vertebrate enzyme, consistent with the significantly diminished cooperativity observed in th

ISSN:0021-2148    

DOI:10.1002/ijch.198600029

出版商:WILEY‐VCH Verlag    

年代:1986

数据来源: WILEY