Biomolecular free energy profiles by a shooting/umbrella sampling protocol, "BOLAS"

A technique called BOLAS for the computation of free energies corresponding to conformational transitions in complex systems was developed by combining a Monte Carlo ensemble of trajectories generated by the shooting algorithm with umbrella sampling. The technique preserved microscopic reversibility and led to correct equilibrium distribution. The technique enabled the 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. The scope of the technique was demonstrated by applying it to the sugar repuckering transition in a solvated deoxyadenosine molecule.