Simulation of conformational changes occurring when a protein interacts with its receptor.
Comput Biol Chem
; 31(3): 196-206, 2007 Jun.
Article
en En
| MEDLINE
| ID: mdl-17500035
ABSTRACT
In order to simulate the conformational changes occurring when a protein interacts with its receptor, we firstly evaluated the structural differences between the experimental unbound and bound conformations for selected proteins and created theoretical complexes by replacing, in each experimental complex, the protein-bound with the protein-unbound chain. The theoretical models were then subjected to additional modeling refinements to improve the side chain geometry. Comparing the theoretical and experimental complexes in term of structural and energetic factors is resulted that the refined theoretical complexes became more similar to the experimental ones. We applied the same procedure within an homology modeling experiment, using as templates the experimental structures of human interleukin-1beta (IL-1beta) unbound and bound with its receptor, to build models of the homologous proteins from mouse and trout in unbound and bound conformations and to simulate the interaction with the related receptors. Our results suggest that homology modeling techniques are sensitive to differences between bound and unbound conformations, and that modeling with accuracy the side chains in the complex improves the interaction and molecular recognition. Moreover, our refinement procedure could be used in protein-protein interaction studies and, also, applied in conjunction with rigid-body docking when is not available the protein-bound conformation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Modelos Moleculares
/
Citocinas
/
Receptores de Citocinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Comput Biol Chem
Asunto de la revista:
BIOLOGIA
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INFORMATICA MEDICA
/
QUIMICA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Italia