title: Quantum mechanical free energy barrier for an enzymatic reaction.
abstract: We discuss problems related to in silico studies of enzymes and show that accurate and converged free energy changes for complex chemical reactions can be computed if a method based on a thermodynamic cycle is employed. The method combines the sampling speed of molecular mechanics with the accuracy of a high-level quantum mechanics method. We use the method to compute the free energy barrier for a methyl transfer reaction catalyzed by the enzyme catechol O-methyltransferase at the level of density functional theory. The surrounding protein and solvent are found to have a profound effect on the reaction, and we show that energies can be extrapolated easily from one basis set and exchange-correlation functional to another. Using this procedure we calculate a barrier of 69 kJ/mol, in excellent agreement with the experimental value of 75 kJ/mol.
authors.affiliation: Department of Theoretical Chemistry, Lund University, Chemical Center, P.O. Box 124, S-22100 Lund, Sweden. Thomas.Rod@teokem.lu.se
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Rod
authors.forename: Ulf
authors.initials: U
authors.lastname: Ryde
mesh_terms: D002394:Catechol O-Methyltransferase / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D009010:Monte Carlo Method; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D002394:Catechol O-Methyltransferase