Modeling enzyme-inhibitor interactions in serine proteases

• Tipo: Artigo em Revista Científica Internacional
• Data: 1999

Autores

Ramos, MJ (Autor) FCUP; Melo, A (Autor) FCUP; Henriques, ES (Autor) Outra; Gomes, JANF (Autor) FCUP; Reuter, N (Autor) Outra; Maigret, B (Autor) Outra; Floriano, WB (Autor) Outra; Nascimento, MAC (Autor) Outra

Revista

Título: International Journal of Quantum Chemistry

Vol. 74

Páginas: 299-314

ISSN: 0020-7608

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 15 Citações

Scopus - 19 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-001-3N0

DOI: 10.1002/(sici)1097-461x(1999)74:3<299::aid-qua3>3.0.co;2-k

Abstract (EN): We are interested in modeling enzyme-inhibitor interactions with a view to improve the understanding of the biology of these processes. The present work focuses, therefore, on the research on enzyme-inhibitor interactions using two highly homologous enzymes as our models: beta-factor XIIa and trypsin. This study so far has focused on the following: (1) arginine-carboxylate interactions such as the one occurring in the "binding pocket" of beta-factor XIIa with an inhibitor; according to the present calculations, the neutral form is usually more stable than is the zwitterion in hydrophobic environments as in the case of the above-mentioned complex. (2) Interactions present in the contact region between trypsin and PTI; the contribution of some amino acids of that region to the binding energy of the complex trypsin-PTI was determined using free-energy simulation methods. (3) Interactions involved in the inhibition of trypsin by PTI; hybrid quantum-classical mechanical calculations (LSCF) were performed to further this point. (C) 1994 John Wiley & Sons, Inc.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 16