Prediction of allosteric sites on protein surfaces with an elastic-network-model-based thermodynamic method.
Phys Rev E Stat Nonlin Soft Matter Phys
; 90(2): 022719, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-25215770
ABSTRACT
Allostery is a rapid and efficient way in many biological processes to regulate protein functions, where binding of an effector at the allosteric site alters the activity and function at a distant active site. Allosteric regulation of protein biological functions provides a promising strategy for novel drug design. However, how to effectively identify the allosteric sites remains one of the major challenges for allosteric drug design. In the present work, a thermodynamic method based on the elastic network model was proposed to predict the allosteric sites on the protein surface. In our method, the thermodynamic coupling between the allosteric and active sites was considered, and then the allosteric sites were identified as those where the binding of an effector molecule induces a large change in the binding free energy of the protein with its ligand. Using the proposed method, two proteins, i.e., the 70 kD heat shock protein (Hsp70) and GluA2 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, were studied and the allosteric sites on the protein surface were successfully identified. The predicted results are consistent with the available experimental data, which indicates that our method is a simple yet effective approach for the identification of allosteric sites on proteins.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Termodinâmica
/
Modelos Moleculares
/
Receptores de AMPA
/
Proteínas de Choque Térmico HSP70
/
Proteínas de Escherichia coli
/
Sítio Alostérico
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article