Coupled semiempirical molecular orbital and molecular mechanics model (QM/MM) for organic molecules in aqueous solution

✍ Scribed by Cummins, Peter L.; Gready, Jill E.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 456 KB
• Volume: 18
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/(sici)1096-987x(199709)18:12<1496::aid-jcc7>3.0.co;2-e

✦ Synopsis

A coupled quantum mechanical and molecular mechanical Ž . QMrMM model based on the AM1, MNDO, and PM3 semiempirical molecular orbital methods and the TIP3P molecular mechanics model for liquid water is presented. The model was parameterized for each of the three molecular orbital methods using the aqueous solvation free energies of a wide range of neutral organic molecules, many of which are representative of amino acid side chains. The fit to the experimental solvation free energies was achieved by varying the Ž . radii in the van der Waals vdW terms for interactions between the solute, Ž . which was treated quantum mechanically, and the molecular mechanics TIP3P solvent molecules. It is assumed that the total free energy can be obtained as the sum of components derived from the electrostatic terms in the Hamiltonian plus a generally smaller ''nonelectrostatic'' term. The electrostatic contributions to Ž . the solvation free energies were computed using molecular dynamics MD simulation and thermodynamic integration techniques; the nonelectrostatic contributions were taken from the literature. It was found that the experimental Ž . free energies could be reproduced accurately to within 1 kcalrmol from the MD simulations, provided that the vdW parameter associated with hydrogen Ž . bonding H bonding was allowed to have different values depending on the Ž . QM method AM1, MNDO, or PM3 and the type of functional group involved in the H bonding. Moreover, the radial distribution functions obtained from the MD simulations using such a parameterization scheme showed the expected H-bonded structures between the solute and molecules of the solvent. The solvent-induced dipole moments also compared favorably with the results of other QMrMM model calculations.