GENETIC ALGORITHMS FOR DOCKING OF ACTINOMYCIN-D AND DEOXYGUANOSINE MOLECULES WITH COMPARISON TO THE CRYSTAL-STRUCTURE OF ACTINOMYCIN D-DEOXYGUANOSINE COMPLEX

Optimal docking of one or two molecules of deoxyguanosine with actinomycin D was predicted theoretically using a genetic algorithm approach. Rather than using a purely geometrical approach, the docking problem was defined in terms of optimization of the intermolecular interaction energy. Efficient location of global intermolecular energy minima is of interest in connection with computer-assisted drug design. The crystal structure of actinomycin D, complexed with two deoxyguanosine molecules, was used as a reference docking structure. The results obtained by genetic algorithm optimization were compared to docking structures refined from the crystal structure using the same force field. Because of their applicability to larger molecules, genetic algorithms demonstrate advantages over conventional optimization methods, which are limited to relatively small molecules with currently available computer resources. The success of locating global minima of this larger molecular complex by genetic algorithms may lead to significant changes in the way drug development is being approached.