A hybrid method for solutes in complex solvents: Density functional theorycombined with empirical force fields

We present a hybrid method for molecular dynamics simulations of solutes in complex solvents as represented, for example, by substrates within enzymes . The method combines a quantum mechanical (QM) description of the solute w ith a molecular mechanics (MM) approach for the solvent. The QM fragment of a simulation system is treated by ab initio density functional theory (DFT ) based on plane- wave expansions. Long-range Coulomb interactions within t he MM fragment and between the QM and the MM fragment are treated by a comp utationally efficient fast multipole method. For the description of covalen t bonds between the two fragments, we introduce the scaled position link at om method (SPLAM), which removes the shortcomings of related procedures. Th e various aspects of the hybrid method are scrutinized through test calcula tions on liquid water, the water dimer, ethane and a small molecule related to the retinal Schiff base. In particular, the extent to which vibrational spectra obtained by DFT for the solute can be spoiled by the lower quality force field of the solvent is checked, including cases in which the two fr agments are covalently joined. The results demonstrate that our QM/MM hybri d method is especially well suited for the vibrational analysis of molecule s in condensed phase. (C) 1999 American Institute of Physics. [S0021-9606(9 9)71521- 7].