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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

EPSP synthase flexibility is determinant to its function: computational molecular dynamics and metadynamics studies

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Autor(es):
Saraiva Macedo Timmers, Luis Fernando ; Neto, Antonio M. S. ; Montalvao, Rinaldo W. ; Basso, Luiz A. ; Santos, Diogenes S. ; de Souza, Osmar Norberto
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: Journal of Molecular Modeling; v. 23, n. 7 JUL 2017.
Citações Web of Science: 0
Resumo

Flexibility is involved in a wide range of biological processes, such as protein assembly and binding recognition. EPSP synthase is an enzyme that must undergo a large conformational change to accommodate its ligands into its binding cavity. However, although the structure of EPSP synthase has been determined, its plasticity has not been explored in depth. Therefore, in this work, we extensively examined the influence of the flexibility of Mycobacterium tuberculosis EPSP (MtEPSP) synthase on the function of this protein using classical and replica-exchange metadynamics simulations. We were able to identify five well-populated conformational clusters for MtEPSP synthase: two corresponding to open, one to ajar, and two to closed conformations. We also pinpointed three hydrophobic regions that are responsible for guiding transitions among these states. Taken together, the new findings presented here indicate how the hydrophobic regions modulate the flexibility of MtEPSP synthase, and they highlight the importance of considering these dynamic features in drug design projects employing this enzyme as a target. (AU)

Processo FAPESP: 11/11343-0 - Usando dados esparsos de ressonância magnética nuclear e modelagem comparativa para determinar estrutura e dinâmica de proteínas com aplicação em desenho racional de drogas
Beneficiário:Rinaldo Wander Montalvão
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 13/18398-0 - Determinação de complexos entre proteínas e ligantes usando dados experimentais esparsos
Beneficiário:Antonio Marinho da Silva Neto
Linha de fomento: Bolsas no Brasil - Doutorado