Relation between sequence and structure of HIV-1 protease inhibitor complexes: a model system for the analysis of protein flexibility.

Détails

ID Serval
serval:BIB_FDECFC9DD1E4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Relation between sequence and structure of HIV-1 protease inhibitor complexes: a model system for the analysis of protein flexibility.
Périodique
Journal of molecular biology
Auteur(s)
Zoete V., Michielin O., Karplus M.
ISSN
0022-2836
Statut éditorial
Publié
Date de publication
2002
Peer-reviewed
Oui
Volume
315
Numéro
1
Pages
21-52
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
Résumé
The flexibility of different regions of HIV-1 protease was examined by using a database consisting of 73 X-ray structures that differ in terms of sequence, ligands or both. The root-mean-square differences of the backbone for the set of structures were shown to have the same variation with residue number as those obtained from molecular dynamics simulations, normal mode analyses and X-ray B-factors. This supports the idea that observed structural changes provide a measure of the inherent flexibility of the protein, although specific interactions between the protease and the ligand play a secondary role. The results suggest that the potential energy surface of the HIV-1 protease is characterized by many local minima with small energetic differences, some of which are sampled by the different X-ray structures of the HIV-1 protease complexes. Interdomain correlated motions were calculated from the structural fluctuations and the results were also in agreement with molecular dynamics simulations and normal mode analyses. Implications of the results for the drug-resistance engendered by mutations are discussed briefly.
Mots-clé
Amino Acid Substitution, Binding Sites, Computer Simulation, Consensus Sequence, Crystallography, X-Ray, Databases, Protein, HIV Protease, HIV Protease Inhibitors, Ligands, Models, Molecular, Motion, Mutation, Pliability, Protein Binding, Protein Conformation
Pubmed
Web of science
Création de la notice
28/01/2008 12:22
Dernière modification de la notice
20/08/2019 17:28
Données d'usage