On Flexible Docking Using Expansive Search

M. Moll, D. Schwarz, A. P. Heath, and L. E. Kavraki, “On Flexible Docking Using Expansive Search,” no. 04-443, 2004.


The activity of most drugs is regulated by the binding of one molecule (the ligand) to a pocket of another, usually larger, molecule, which is commonly a protein. This report describes a new approach to creating low-energy structures of flexible proteins to which ligands can be docked. The flexibility of molecules is encoded with thousands of parameters making the search for valid complexes a formidable problem. Our method takes into account the flexibility of the protein as this can be encoded by its major modes of motion. The output of the program consists of low-energy protein conformations that can then be docked with a ligand using a traditional docking program. We employ a robotics-based approach for exploring the conformational space of the protein. Our long term goal is to develop an efficient, accurate, and automated algorithm that will be used to screen large databases of molecules for novel therapeutics.