ABSTRACT

Central to the success of any computational approach to the study of chemical systems is the quality of the mathematical model used to calculate the energy of the system as a function of its structure. For smaller chemical systems studied in the gas phase, quantum mechanical (QM) approaches are appropriate. The success of these methods was emphasized by the selection of John A. Pople and Walter Kohn as winners of the 1998 Nobel prize in chemistry. These methods, however, are typically limited to systems of approximately 100 atoms or less, although approaches to treat large systems are under development [1]. Systems of biochemical or biophysical interest typically involve macromolecules that contain 1000-5000 or more atoms plus their condensed phase environment. This can lead to biochemical systems containing 20,000 atoms or more. In addition, the inherent dynamical nature of biochemicals and the mobility of their environments [2,3] require that large number of conformations, generated via various methods (see Chapters 3, 4, 6, and 10), be subjected to energy calculations. Thus, an energy function is required that allows for 106 or more energy calculations on systems containing on the order of 105 atoms.