Molecular mechanics energy function

Force-field-based scoring functions use arbitrary empirical estimates of interaction energies obtained by molecular mechanics energy functions. This simple approximation, which takes into account only enthalpic contribution often correlates well with the experiment. Solvent effects are described by atom-based solvation parameters, which are computed for the surface of both ligand and receptor which is buried upon complexation. DOCK-chemical27 and CHARMm scoring functions represent this class. 

Brodmeier and Pretsch have used a GA to perform molecular minimization using a molecular mechanics energy function. The GA encodes torsional angles as binary numbers in each individual. Hermann and Suhai use a similar encoding, but use the MOPAC AMI Hamiltonian in their fitness function. Using the same encoding Meza and co-workers found that GAs and a direct search method were equally effective and efficient at energy minimization. This work was a continuation of an earlier study on model 2D systems. ... 

A vast amount of empirical molecular potential energy functions and a series of corresponding programs (molecular mechanics and consistent force field programs) are available (for recent reviews see 203 205)). Unfortunately these energy functions are always the result of optimization on a rather limited group of compounds. No... 

A related study on the addition of OH to formamide in water by Weiner et al. should be noted.They obtained potential functions from quantum mechanical calculations and estimated the solvent effect by molecular mechanics energy minimization for the reacting system in a box of TIP3P water. The latter procedure does not provide proper configurational averaging. Nevertheless the computed and AE in water of 22 and 9 kcal/mol are consistent with experimental data on the hydrolyses of amides. As in the present case, the transition state in water is very productlike and is computed to occur at a C-O distance of about 2.0 A. 

Many molecular modelling techraques that use force-field models require the derivatives of the energy (i e the force) to be calculated with respect to the coordinates. It is preferable that analytical expressions for these derivatives are available because they are more accurate and faster than numerical derivatives. A molecular mechanics energy is usually expressed in terms of a combination of internal coordinates of the system (bonds, angles, torsions, etc.) and interatomic distances (for the non-bonded interactions). The atomic positions in molecular mechanics are invariably expressed in terms of Cartesian coordinates (unlike quantum mechanics, where internal coordinates are often used). The calculation of derivatives with respect to the atomic coordinates usually requires the chain rule to be applied. For example, for an energy function that depends upon the separation between two atoms (such as the Lennard-Jones potential. Coulomb electrostatic interaction or bond-stretching term) we can write ... 

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