A Bayesian Optimization Algorithm for De Novo ligand design based docking running over GPU

A principal fragment-based design approach is De Novo ligand design at which small-molecule structures from a database of existing compounds (or compounds that could be made) are docked into the protein binding site following a virtual synthesis scheme. New virtual structures can easily be constructed from combinatorial building blocks. Typically, tens of thousands of orientations are generated for each ligand candidate, therefore global optimization algorithms are usually employed to search the chemical space by generating new molecular structures through probing many different fragments in a combinatorial fashion. We propose using Bayesian Optimization Algorithm (BOA), a meta-heuristic algorithm, in searching the combination of pre-docked fragments through minimizing the energy of ligand-receptor docking. We further introduce the use of GPU (Graphical Processing Unit) to overcome the very long time required in evaluating each possible fragment combination. We show how the GPU utilization enables experimenting larger fragments and target receptors for more complex instances. The experiments resulted in regenerating three drug-like compounds defined in the ZINC database as well as finding a new compound. The Results show how the nVidia´s Tesla C1060 GPU was utilized to accelerate the docking process by two orders of magnitude.