Radhakrishnan Ravi, Schlick Tamar
Department of Chemistry, New York University, New York, NY 10012, USA.
J Chem Phys. 2004 Aug 1;121(5):2436-44. doi: 10.1063/1.1766014.
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.
我们通过将射击算法生成的轨迹的蒙特卡罗系综与伞形采样相结合，开发了一种用于计算复杂系统中构象转变对应自由能的高效技术。受过渡路径采样方法的启发，我们的方案“BOLAS”（以牛仔的套索命名）保持微观可逆性，并导致正确的平衡分布。与传统的力偏置伞形采样协议相比，这使得能够以更低的系统误差计算生物分子系统沿复杂反应坐标的自由能分布。我们证明了BOLAS对于双稳势的有效性，并通过将其应用于溶剂化脱氧腺苷分子中的糖重 puckering 转变来说明该方法的适用范围。
