Determination of AMBER force field parameters for carborane moiety using quantum chemical calculations

Abstract

Because the hydrophobic effects play important roles in the formations of drug-target complexes, stable and bulky hydrophobic groups are useful for drug design trials. Carborane, which is one of the boron cluster, is expected to be useful for drug design trials as the novel hydrophobic moiety. On the other hand, force field parameters for boron are not sufficiently developed. Because the force field parameters are indispensable to classical molecular mechanics calculations, in silico drug design trials using classical mechanical methods were occasionally inapplicable to carborane derivatives. In this study, force field parameters of carborane moiety were determined using quantum chemical calculations. Because the bond lengths and angles cannot change independently in the carborane structure, multiple regression analyses were used. The atoms in carborane were slightly moved, and the changes of energies were calculated by quantum chemical calculations. The multiple regression analyses using structural features, e.g. angles and bond lengths, as independent variables and quantum chemically calculated enegies of the structures as dependent variables were carried out to determine the force field parameters.