Modeling enzyme-inhibitor interactions in serine proteases

• Type: Article in International Scientific Journal
• Date: 1999

Authors

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

Journal

Title: International Journal of Quantum Chemistry

Vol. 74

Pages: 299-314

ISSN: 0020-7608

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 15 Citations

Scopus - 19 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16