ISSN:0094-243X    

DOI:10.1063/1.41333

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

During the last decade it has become feasible to simulate the behaviour of biologically relevant molecules on a computer. These simulations are extremely demanding in terms of computer time. A great variety of time‐saving techniques has been and is still being developed. These are reviewed.

ISSN:0094-243X    

DOI:10.1063/1.41334

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Molecular dynamics simulations are used to study the dynamics of carbon monoxide following its photodissociation from the protein in myoglobin. The role of the protonation state of the distal histidine and its effect on the dynamics and conformation of the unbound ligand are determined. Analysis of the center‐of‐mass, rotational, and vibrational dynamics of the ligand agrees well with the experimental data of Anfinrud, Han and Hochstrasser [Proc. Natl. Acad. Sci. USA86, 8387 (1989)].

ISSN:0094-243X    

DOI:10.1063/1.41335

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Two computational approaches to study plausible conformations of biological molecules and the transitions between them are presented and discussed. The first approach is a new search algorithm which enhances the sampling of alternative conformers using a mean field approximation. It is argued and demonstrated that the mean field approximation has a small effect on thelocationof the minima. The method is a combination of the LES protocol (Locally Enhanced Sampling) and simulated annealing. The LES method was used in the past to study the diffusion pathways of ligands from buried active sites in myoglobin and leghemoglobin to the exterior of the protein. The present formulation of LES and its implementation in a Molecular Dynamics program is described. An application for side chain placement in a tetrapeptide is presented. The computational effort associated with conformational searches using LES grows only linearly with the number of degrees of freedom, whereas in the exact case the computational effort grows exponentially. Such saving is of course associated with a mean field approximation. The second branch of studies pertains to the calculation of reaction paths in large and flexible biological systems.An extensive mapping of minima and barriers for two different tetrapeptides is calculated from the known minima and barriers of alanine tetrapeptide which we calculated recently.1The tetrapeptides are useful models for the formation of secondary structure elements since they are the shortest possible polymers of this type which can still form a complete helical turn. The tetrapeptides are isobutyryl‐val(&khgr;1=60)‐ala‐ala and isobutyryl‐val(&khgr;1=−60)‐ala‐ala. Properties of the hundreds of minima and of the hundreds intervening barriers are discussed. Estimates for thermal transition times between the many conformers (and times to explore the complete phase space) are calculated and compared. It is suggested that the most significant effect of the side chain size is on thenumberof the direct paths between the minima. The influence on the distribution of the barriers and the minima energies is less significant. Calculation of reaction paths inlargemolecular systems requires new computational techniques. We employed our newly developed reaction path algorithm (SPW) for the study of the B to Z transition in DNA. The SPW (Self Penalty Walk) algorithm is explained in detail. A complex reaction coordinate (the B to Z transition in DNA) is calculated and analyzed. The calculated reaction path is for six basepairs DNA (including all 376 atoms). The path consists of 180° flips of two basepairs from the B DNA conformation to the Z DNA conformation.

ISSN:0094-243X    

DOI:10.1063/1.41336

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

In this article we review the results of our applications of MD simulations with specialized sampling techniques to the study of secondary structural stability in solution. We present free energy surfaces as functions of conformational reaction coordinates which correspond to the folding (and unfolding) of several model secondary structures: an isolated amide hydrogen bond, reverse turns in blocked di‐amino acids, &agr; helices in blocked tri‐ and tetra‐amino acids, and an antiparallel &bgr; sheet formed by two blocked amino acids. The free energy surfaces allow us to identify stable structures along the reaction coordinates and, in some cases, to estimate the timescales for the interconversion of these structures. Furthermore, we use thermodynamic decompositions of free energy differences taken from the surfaces to understand the differences of the relative stabilities of various folded and unfolded structures in terms peptide‐peptide and peptide‐solvent interactions. The results presented herein should be useful for evaluating the contributions of secondary structures to the stabilities of folded proteins, and for developing a microscopic picture of the role of secondary structure formation in the mechanism of protein folding.

ISSN:0094-243X    

DOI:10.1063/1.41337

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

A framework for thinking about protein structure prediction schemes based on analogies to spin glasses and neural networks is reviewed. The ideas of biological invariances and of pattern filtration for generalization are discussed and evaluated for an example of recognizing a cytochrome structure.

ISSN:0094-243X    

DOI:10.1063/1.41338

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

A new approach to generation of tertiary conformations for a protein of given primary sequence is reviewed. Amino acid pair potentials are derived based on the hypothesis that the observed pair correlation function for a given pair of amino acids is distributed according to a Boltzmann probability distribution. Tests of this idea have been reported by Wilson and Doniach for folding of a small protein and by Sippl and collaborators for discriminating a correctly folded protein from a set of artificially misfolded models. Preliminary tests are reported on the use of this approach for the antibody‐antigen docking problem and for exploration of conformation space of a polypeptide loop using a Langevin dynamics approach.

ISSN:0094-243X    

DOI:10.1063/1.41340

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.41349

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.41350

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.41351

出版商:AIP    

年代:1991

数据来源: AIP