The intramolecular mechanism for the second proton transfer in triosephosphate isomerase (TIM) : a QM/FE approach
Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 1: 46-56, 2003
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 24(2003), 1 vom: 15. Jan., Seite 46-56 |
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| Weitere Verfasser: | , |
| Format: | Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2003
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Protons Triose-Phosphate Isomerase EC 5.3.1.1 |
| Zusammenfassung: | Copyright 2002 Wiley Periodicals, Inc. J Comput Chem 1: 46-56, 2003 The intramolecular mechanism we earlier proposed [Alagona, G.; Desmeules, P.; Ghio, C.; Kollman, P. A. J Am Chem Soc 1984, 106, 3623] for the second proton transfer of the reaction catalyzed by triosephosphate isomerase (TIM) is examined ab initio at the HF and MP2/6-31+G** levels in vacuo for two conformers of the enediolate phosphate (ENEP), with the ethereal oxygen of the phosphate group either syn (X), as in the crystal structure, or anti (Y) with respect to the enediolate carbonyl O. The barrier height for the intramolecular proton transfer occurring in enediolate is very sensitive to electron correlation corrections. The MP2 internal energy barrier is much lower than the HF one, while the free energy (FE) barrier is even more favorable, indicating that the enzyme presence is not requested to speed up that step. An investigation of the dynamical aspects of the mechanism, along the pathway from ENEP A (with H on O(1)) to TS and from TS to ENEP B (with H on O(2)), was, however, carried out in the presence of the enzyme field while using a neutral His-95 with its proton on Ndelta. To perform the FE simulations, it was necessary to parametrize in the AMBER force-field the ENEP A, TS and B species, whose partial charges have been determined with the RESP procedure, with the X and Y arrangements of the phosphate head. Actually, the FE/QM approach produced a low barrier and a substantial balance between A and B, especially at the MP2 level. The trajectories, analyzed paying a particular attention to the positions assumed by His-95 and by the other active site residues, put forward somewhat different H-bond patterns around the X or Y enediolate phosphate |
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| Beschreibung: | Date Completed 20.06.2003 Date Revised 16.12.2002 published: Print Citation Status MEDLINE |
| ISSN: | 1096-987X |