ISSN:0094-243X    

DOI:10.1063/1.41309

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

This lecture starts with a survey of the present state of knowledge on the topology of potential hypersurfaces of proteins, on transitions in conformational space, and on harmonic and quasi‐harmonic methods of analysis of sub‐state properties. The concepts of deterministic vs ergodic behaviour of the paths actually followed in conformational space are discussed. The possible connection between selectivity (or ‘‘accuracy’’) in enzyme catalysis and the time structure of conformational transitions is shown. In a second part, two different methods used by the authors for theoretical computation of conformational paths linking known crystallographic structures in citrate synthase are commented: an implementation of Elber and Karplus’ chain algorithm, and a new method which we named directed dynamics. In connection with the ‘‘multiple minima problem’’, the occurrence of lower and upper bounds in the temperatures used in molecular dynamics searches of conformational minima is discussed with emphasis on their dependence with respect to the effective number of degrees of freedom in the conformational space investigated. Finally, a hint on the total transition time is given.

ISSN:0094-243X    

DOI:10.1063/1.41310

出版商:AIP    

年代:1991

数据来源: AIP

ISSN:0094-243X    

DOI:10.1063/1.41311

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Molecular dynamics simulations have been used to compute the difference in is replaced by Ala. They yield results (−3.42/−5.21 kcal/mol) that compared favorably with the experimental values (−3.3/−4.0 kcal/mol). The major contributions to the free energy difference arise from bonding terms involving degrees of freedom of the mutated sidechain, and from non‐bonded interactions of that sidechain with its environment in the folded protein. By comparison with simulations of an extended peptide in the absence of solvent, used as a reference state, it is shown that hydration effects play a minor role in the overall free energy balance of the Ile to Ala transformation.

ISSN:0094-243X    

DOI:10.1063/1.41312

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Artificial neural networks are cognitive computational strategies which involve training on well‐established examples rather than programming of the traditional sequential type. They are already enjoying considerable success with the prediction of protein secondary structures, and preliminary results with tertiary structures, though less impressive, nevertheless provide grounds for optimism.

ISSN:0094-243X    

DOI:10.1063/1.41313

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Methodological aspects of solvent effects, simulation protocol, analysis and visualization of results, accuracy, and sensitivity of results to force field parametrization are discussed for molecular dynamics simulation on oligonucleotides. Recent results comparing AMBER, CHARMM and GROMOS force fields are included. The calculation of build‐up curves for the nuclear Overhauser effect from simulations is also described.

ISSN:0094-243X    

DOI:10.1063/1.41314

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Only about 1/20 of DNA of higher organisms codes for proteins, by means of classical triplet code. The rest of DNA sequences is largely silent, with unclear functions, if any. The triplet code is not the only code (message) carried by the sequences. There are three levels of molecular communication, where the same sequence ‘‘talks’’ to various bimolecules, while having, respectively, three different appearances: DNA, RNA and protein. Since the molecular structures and, hence, sequence specific preferences of these are substantially different, the original DNA sequence has to carry simultaneously three types of sequence patterns (codes, messages), thus, being a composite structure in which one had the same letter (nucleotide) is frequently involved in several overlapping codes of different nature. This multiplicity and overlapping of the codes is a unique feature of the Gnomic, language of genetic sequences. The coexisting codes have to be degenerate in various degrees to allow an optimal and concerted performance of all the encoded functions. There is an obvious conflict between the best possible performance of a given function and necessity to compromise the quality of a given sequence pattern in favor of other patterns. It appears that the major role of various changes in the sequences on their ‘‘ontogenetic’’ way from DNA to RNA to protein, like RNA editing and splicing, or protein post‐translational modifications is to resolve such conflicts. New data are presented strongly indicating that the gene splicing is such a device to resolve the conflict between the code of DNA folding in chromatin and the triplet code for protein synthesis.

ISSN:0094-243X    

DOI:10.1063/1.41315

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

Biological activities of halogenated dibenzo‐p‐dioxins include toxicity and aryl hydrocarbon hydroxilase (AHH) induction. The available evidences1indicate that both types of activity are receptor‐mediated via an initial ‘‘recognition’’ step.

ISSN:0094-243X    

DOI:10.1063/1.41317

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

A methodology based on molecular modeling and chemometrics [1] has been applied for the identification of the geometrical pharmacophore in a series of inhibitors of HMG‐CoA, an enzyme involved in cholesterol biosynthesis.

ISSN:0094-243X    

DOI:10.1063/1.41318

出版商:AIP    

年代:1991

数据来源: AIP

摘要:

The possibility of using informational calculations to establish relationships between chemical structures of molecules and their biological activities and to classify biomolecules is studied here.

ISSN:0094-243X    

DOI:10.1063/1.41319

出版商:AIP    

年代:1991

数据来源: AIP