Force-field parameters for the simulation of tetrahedral intermediates of serine hydrolases.
CHARMM force-field parameters are reported for the tetrahedral intermediate of serine hydrolases. The fitting follows the standard protocol proposed for CHARMM22. The reference data include ab initio (RHF/6-31G*) interaction energies of complexes between water and the model compound 1,1-dimethoxyethoxide, torsional profiles of related model compounds from correlated ab initio (MP2/6-311+G*//B3LYP/6-31+G*) calculations, as well as molecular geometries and vibrational frequencies from density functional theory (B3LYP/6-31+G*). The optimized parameters reproduce the target data well. Their utility is demonstrated by a QM/MM study of the tetrahedral intermediate in Bacillus subtilis lipase A, and by classical molecular modeling of enantioselectivity in Pseudomonas aeruginosa lipase and its mutants.
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
Nikolaj
N
Otte
Marco
M
Bocola
Walter
W
Thiel
D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D012697:Serine Endopeptidases / Q000737:chemistry*; D014867:Water / Q000737:chemistry
D001426:Bacterial Proteins; D014867:Water; D012697:Serine Endopeptidases