Foundations of Molecular Mechanics

Molecular mechanics force fields rest on four fundamental principles. The first principle is derived from the Bom-Oppenheimer approximation. Electrons have much lower mass than nuclei and move at much greater velocity. The velocity is sufficiently different that the nuclei can be considered stationary on a relative scale. In effect, the electronic and nuclear motions are uncoupled, and they can be treated separately. Unlike quantum mechanics, which is involved in determining the probability of electron distribution, molecular mechanics focuses instead on the location of the nuclei. Based on both theory and experiment, a set of equations are used to account for the electronic-nuclear attraction, nuclear-nuclear repulsion, and covalent bonding. Electrons are not directly taken into account, but they are considered indirectly or implicitly through the use of potential energy equations. This approach creates a mathematical model of molecular structures which is intuitively clear and readily available for fast computations. The set of equations and constants is defined as the force 

The third principle relates to the set of equations which describe the potential energy surface of the molecule. These potential energy equations, derived primarily from classical physics, contain parameters optimized to obtain the best match between experimental data and/or theoretical results for a training set of compounds. Once the parameters are evaluated for a set of structures (as diverse as possible), they are fixed and then used unmodified for other similar (and usually larger) compounds. As a first approximation, these parameters must be transferable from one structure to another for this method to work and be generally applicable. 

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