Generalized Multipole Moments and Polarizabilities, and their Use in Ultrafast Quantum Mechanics/Molecular Mechanics Monte Carlo Simulation of Solutions

by Janowski, Tomasz; Pulay, Peter

Most chem. and virtually all biochem. takes place in soln., often in highly polar solvents like water. The general method to model such systems quantum mech. is to use accurate quantum calcns. for the solute, and mol. mechanics for the solvent (or protein environment). The large no. of solvent configurations (millions) required to obtain converged thermodn. data poses strict limits on this technique. As the interaction between the solute and solvent is largely electrostatic, it is possible to precalc. the first and second order response of the solute to the elec. potential of the solvent. The latter is represented by a Fourier expansion within the solute mol. or fragment. This is a generalization of the multipole representation of elec. moments and polarizabilities which expands the potential in solid spherical harmonics, but is applicable only for small solutes. The first-order response is calcd. from the field of the solute at the MM charges. We have implemented first and second order responses in the PQS package, using Monte Carlo simulation for the solvent. Previous work was limited to the first-order. Neglecting the second order response introduces significant errors, as shown in Fig. 1 for guanine (RHF/6-31G*) dissolved in TIP3P water. Both the abs. value and the scatter of the energy error, compared to full quantum mech. calcns. for the solute (guanine) is greatly reduced if polarizability is included, compared to first order (interaction between fixed charges). Third order effects are negligible. Our procedure accelerates the averaging process by 3-4 orders of magnitude without introducing noticeable errors.