GLOBAL ENERGY MINIMIZATION OF SMALL MOLECULES COMBINING CONSTRAINT LOGIC PROGRAMMING AND MOLECULAR MECHANICS

The paper presents an approach to molecular energy minimization using Constraint Logic Programming (CLP) as a preprocessor to a molecular me chanics minimization program such as CHARMM. The use of CLP enables th e definition of simple constraints that sufficiently describe relation s in a molecule, thus limiting the search space of the globally optima l solution. The approach was used on the problem of minimizing the ene rgy of the alanine dipeptide and N-methylalanylacetamide. An approxima te 3-D structure produced by a CLP system was used as an initial struc ture for the CHARMM program that considers all relations in such a str ucture and performs energy optimization With this initial structure, c omputed in about 1 min of CPU time, the optimal solution (global minim um) was found in only a few seconds, while calculating the same soluti on with CHARMM alone took 15 h. All calculation were performed on HP/7 35.