Specific parametrisation of a hybrid potential to simulate reactions in phosphatases

Autor(es)

Arantes, GM ; Loos, M

• Tipo de documento: Artigo Científico
• Fonte: Physical Chemistry Chemical Physics; v. 8, n. 3, p. 347-353, JAN 21 2006.
• Citações Web of Science: 21

Resumo

Phosphatases are key biomolecules because they regulate many cellular processes. These enzymes have been studied for many years, but there are still doubts about the catalytic mechanism. Computer simulations can be used to shed light on these questions. Here we develop a new and specific parametrisation, and present extensive tests of a hybrid potential that can be used to reliably simulate reactions catalysed by phosphatases. High level ab initio data for phosphate ester thiolysis and alcoholysis is used in the training set. The parametrised quantum mechanical Hamiltonian reproduces ab initio energies with a root mean-squared deviation of 3 kcal mol(-1) for species along the pathway of various phosphate ester reactions. Preliminary results for simulation with the calibrated hybrid potential of catalysis by the phosphatase VHR indicate the calculated reaction barriers are in very good agreement with experiment. (AU)

• Processo FAPESP: 99/04072-7 - Mecanismos da tiólise de ésteres de fosfato: modelos da fosfatase ácida SH-dependente
• Beneficiário: Guilherme Menegon Arantes
• Modalidade de apoio: Bolsas no Brasil - Doutorado