Biomolecular free energy profiles by a shooting/umbrella sampling protocol, "BOLAS".
We develop an efficient technique for computing free energies corresponding to conformational transitions in complex systems by combining a Monte Carlo ensemble of trajectories generated by the shooting algorithm with umbrella sampling. Motivated by the transition path sampling method, our scheme "BOLAS" (named after a cowboy's lasso) preserves microscopic reversibility and leads to the correct equilibrium distribution. This makes possible computation of free energy profiles along complex reaction coordinates for biomolecular systems with a lower systematic error compared to traditional, force-biased umbrella sampling protocols. We demonstrate the validity of BOLAS for a bistable potential, and illustrate the method's scope with an application to the sugar repuckering transition in a solvated deoxyadenosine molecule.
Radhakrishnan
Ravi
R
Department of Chemistry, New York University, New York, NY 10012, USA.
Schlick
Tamar
T
D000465:Algorithms; D001703:Biophysics / Q000379:methods*; D002241:Carbohydrates / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003839:Deoxyadenosines / Q000737:chemistry; D015233:Models, Statistical; D008962:Models, Theoretical; D009010:Monte Carlo Method; D012984:Software; D013816:Thermodynamics
D002241:Carbohydrates; D003839:Deoxyadenosines