Exploring Conformational Space with Thermal Fluctuations Obtained by Normal-Mode Analysis.
J Chem Inf Model
; 60(6): 3068-3080, 2020 06 22.
Article
em En
| MEDLINE
| ID: mdl-32216314
ABSTRACT
Proteins in their native states can be represented as ensembles of conformers in dynamical equilibrium. Thermal fluctuations are responsible for transitions between these conformers. Normal-modes analysis (NMA) using elastic network models (ENMs) provides an efficient procedure to explore global dynamics of proteins commonly associated with conformational transitions. In the present work, we present an iterative approach to explore protein conformational spaces by introducing structural distortions according to their equilibrium dynamics at room temperature. The approach can be used either to perform unbiased explorations of conformational space or to explore guided pathways connecting two different conformations, e.g., apo and holo forms. In order to test its performance, four proteins with different magnitudes of structural distortions upon ligand binding have been tested. In all cases, the conformational selection model has been confirmed and the conformational space between apo and holo forms has been encompassed. Different strategies have been tested that impact on the efficiency either to achieve a desired conformational change or to achieve a balanced exploration of the protein conformational multiplicity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Argentina