A methodology for efficiently sampling the conformation space of molecular structures

Abstract

Motivated by recently developed computational techniques for studying protein flexibility, and their potential applications in docking, we propose an efficient method for sampling the conformational space of complex molecular structures. We focus on the loop closure problem, identified in the work of Thorpe and Lei (2004 Phil. Mag. 84 1323–31) as a primary bottleneck in the fast simulation of molecular motions. By modeling a molecular structure as a branching robot, we use an intuitive method in which the robot holds onto itself for maintaining loop constraints. New conformations are generated by applying random external forces, while internal, attractive forces pull the loops closed. Our implementation, tested on several model molecules with low number of degrees of freedom but many interconnected loops, gives promising results that show an almost four times speed-up on the benchmark cube-molecule of Thorpe and Lei.