ABSTRACT
The molecular mechanics (MM) method is well established in organic chemistry (1-4). For many types of molecules, reliable structures can be generated quickly and conformational energies can be calculated with a high degree of accuracy (5). Combination of force field methods with dynamic or stochastic schemes allows determination of thermodynamic and solvation properties (1-3). Force fields are routinely applied to large systems, consisting of several thousand atoms. It is also possible to perform exhaustive searches for low-energy conformations of molecules with 10-20 freely rotatable bonds (6). Compared to computational methods based on quantum mechanical (QM) calculations, force field methods are limited in scope, since only systems with identical bonding (i.e., conformers or diastereomers) can be directly compared. However, within this limitation, force fields are several orders of magnitude faster than any QM method. In addition, when high-quality parameters are available, the accuracy of force fields is com petitive with standard QM methods, such as MP2 and B3LYP, and better than semiempirical schemes (5).
