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Modeling enzyme–inhibitor interactions in serine proteases
Author(s) -
Ramos Maria João,
Melo André,
Henriques Elsa S.,
Gomes José A. N. F.,
Reuter Nathalie,
Maigret Bernard,
Floriano Wely B.,
Nascimento Marco A. C.
Publication year - 1999
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1999)74:3<299::aid-qua3>3.0.co;2-k
Subject(s) - trypsin , zwitterion , chemistry , proteases , enzyme , serine , carboxylate , trypsin inhibitor , amino acid , arginine , biochemistry , computational chemistry , stereochemistry , organic chemistry , molecule
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: β‐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 β‐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. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 74: 299–314, 1999