Ultrafast Quantum Mechanics/Molecular Mechanics Monte Carlo simulations using generalized multipole polarizabilities

by Janowski, T.; Wolinski, K.; Pulay, P.

A fast and accurate Quantum Mechanics/Molecular Mechanics method is described for thermodynamic simulation of solutes (or active sites in flexible molecules) in polar environments. The solute is described quantum mechanically and is held fixed during averaging over solvent configurations, which are described by Molecular Mechanics. Quantum calculations during simulation are replaced by the evaluation of the response of the solute to the long range electric field of the solvent, using precalculated generalized electric moments and polarizabilities. This results in huge decrease of computational time without affecting the accuracy of the QM/MM results. Implementation in a Monte Carlo program accelerated the simulations of guanine and the phenylalanine dipeptide in TIP3P water by over four orders of magnitude. Polarizability is essential for accuracy. Its inclusion decreases the average signed energy error and its standard deviation from 5.69 to 0.003 and 1.22 to 0.013 kcal/mol, respectively, for the dipeptide. Hyperpolarizability contributions are insignificant.

Journal
Chemical Physics Letters
Volume
530
Year
2012
Start Page
1-9
URL
https://dx.doi.org/10.1016/j.cplett.2012.01.008
ISBN/ISSN
1873-4448; 0009-2614
DOI
10.1016/j.cplett.2012.01.008