Molecular properties from combined QM/MM methods. I. Analytical second derivative and vibrational calculations

Analytical second derivatives for combined QM/MM calculations have been for mulated and implemented in the CHARMM program interfaced with the ab initio quantum mechanical GAMESS and CADPAC programs. This makes possible evaluat ion of vibrational frequencies and infrared intensities in large systems th at cannot be treated effectively by QM or MM alone; examples are polarizabl e molecules in solution and substrates or transition states in enzymes. Tes t calculations on a number of systems, including formamide in water, butano l, a model transition state structure for triosephosphate isomerase and the active site model of myoglobin, show that the MM description of the enviro nment can capture much of its polarization effects on the QM region. Thus t he implementation of analytical second derivatives within the QM/MM framewo rk has considerable potential for the study of large systems. (C) 2000 Amer ican Institute of Physics. [S0021-9606(99)30548-1].