Specific parametrisation of a hybrid potential to simulate reactions in phosphatases.
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.
Instituto de Química, Universidade de São Paulo, Av. Lineu Prestes 748, São Paulo, SP 05508-900, Brasil. gma@dinamicas.art.br
Guilherme Menegon
GM
Arantes
Michel
M
Loos
D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003198:Computer Simulation; D004563:Electrochemistry; D015394:Molecular Structure; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory
D000596:Amino Acids; D010744:Phosphoric Monoester Hydrolases