Global Energy Minimization of Small Molecules Combining Constraint Logic Programming and Molecular Mechanics

Abstract

The paper presents an approach to molecular energy minimization using Constraint Logic Programming (CLP) as a preprocessor to a molecular mechanics minimization program such as CHARMM. The use of CLP enables the definition of simple constraints that sufficiently describe relations in a molecule, thus limiting the search space of the globally optimal solution. The approach was used on the problem of minimizing the energy of the alanine dipeptide and N-methylalanylacetamide. An approximate 3-D structure produced by a CLP system was used as an initial structure for the CHARMM program that considers all relations in such a structure and performs energy optimization. With this initial structure, computed in about 1 min of CPU time, the optimal solution (global minimum) was found in only a few seconds, while calculating the same solution with CHARMM alone took 15 h. All calculations were performed on HP/735.