Implementation of the IMOMM methodology for performing combined QM/MM molecular dynamics simulations and frequency calculations

A technique for implementing the integrated molecular orbital and molecular mechanics (IMOMM) methodology developed by Maseras and Morokuma that is us ed to perform combined quantum mechanics/molecular mechanics (QM/MM) molecu lar dynamics simulations, frequency calculations and simulations of macromo lecules including explicit solvent is presented. Although the IMOMM methodo logy is generalized to any coordinate system, the implementation first desc ribed by Maseras and Morokuma requires that the QM and MM gradients be tran sformed into internal coordinates before they are added together. This coor dinate transformation can be cumbersome for macromolecular systems and can become ill-defined during the course of a molecular dynamics simulation. We describe an implementation of the IMOMM method in which the QM and MM grad ients are combined in the cartesian coordinate system, thereby avoiding pot ential problems associated with using the internal coordinate system. The i mplementation can be used to perform combined QM/MM molecular dynamics simu lations and frequency calculations within the IMOMM framework. Finally, we have examined the applicability of thermochemical data derived from IMOMM f ramework. Finally, we have examined the applicability of thermochemical dat a derived from IMOMM frequency calculations.