Basic Strategies for Molecular Docking with Scoring Functions
Gwyn Skone, Stephen Cameron, and Irina Voiculescu
In recent years, the potential benefits from high-throughput virtual screening to the drug discovery community have been recognized, bringing an increase in the number of tools developed for this purpose. These programs have to process large quantities of data, searching for an optimal solution in a vast combinatorial range. This is particularly the case for protein-ligand docking 1. Proteins are sophisticated structures, with complicated ligand-interactions for which either molecule might reshape itself 2,3. Even the very limited flexibility model of rigid conformation lists requires a 7-dimensional exploration, and the functions for evaluating pose suitability can be quite complex to calculate 4.
This work brings a pure computer science approach to the field, hoping to improve the speed and accuracy of such tools by exploring principles of function evaluation in the context of an existing commercial docking program. We present some early results from this project, demonstrating a substantial reduction in run time and some improvement to ligand placement.