A Java-based platform, MoleGear, is developed for de novo molecular design based on the chemistry development kit (CDK) and other Java packages. MoleGear uses evolutionary algorithm (EA) to explore chemical space, and a suite of fragment-based operators of growing, crossover, and mutation for assembling novel molecules that can be scored by prediction of binding free energy or a weighted-sum multi-objective fitness function. The EA can be conducted in parallel over multiple nodes to support large-scale molecular optimizations. Some complementary utilities such as fragment library design, chemical space analysis, and graphical user interface are also integrated into MoleGear. The candidate molecules as inhibitors for the human immunodeficiency virus 1 (HIV-1) protease were designed by MoleGear, which validates the potential capability for de novo molecular design.
Keywords: de novo design; drug molecules; evolutionary algorithm; fitness; multi-objective function.