title: A General, Adaptive, Roadmap-Based Algorithm for Protein Motion Computation.
abstract: Precious information on protein function can be extracted from a detailed characterization of protein equilibrium dynamics. This remains elusive in wet and dry laboratories, as function-modulating transitions of a protein between functionally-relevant, thermodynamically-stable and meta-stable structural states often span disparate time scales. In this paper we propose a novel, robotics-inspired algorithm that circumvents time-scale challenges by drawing analogies between protein motion and robot motion. The algorithm adapts the popular roadmap-based framework in robot motion computation to handle the more complex protein conformation space and its underlying rugged energy surface. Given known structures representing stable and meta-stable states of a protein, the algorithm yields a time- and energy-prioritized list of transition paths between the structures, with each path represented as a series of conformations. The algorithm balances computational resources between a global search aimed at obtaining a global view of the network of protein conformations and their connectivity and a detailed local search focused on realizing such connections with physically-realistic models. Promising results are presented on a variety of proteins that demonstrate the general utility of the algorithm and its capability to improve the state of the art without employing system-specific insight.
authors: Kevin
authors: K
authors: Molloy
authors: Amarda
authors: A
authors: Shehu
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D008962:Models, Theoretical; D009038:Motion; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012371:Robotics; D013269:Stochastic Processes; D013816:Thermodynamics
chemical_list: D011506:Proteins