ct300978b_si_001.pdf (5.31 MB)

Self-Learning Adaptive Umbrella Sampling Method for the Determination of Free Energy Landscapes in Multiple Dimensions

Download (5.31 MB)
journal contribution
posted on 19.02.2016, 12:36 by Wojciech Wojtas-Niziurski, Yilin Meng, Benoı̂t Roux, Simon Bernèche
The potential of mean force describing conformational changes of biomolecules is a central quantity for understanding the function of biomolecular systems. Calculating an energy landscape of a process that depends on three or more reaction coordinates requires extensive computational power, making some multidimensional calculations practically impossible. Here, we present an efficient automatized umbrella sampling strategy for calculating a multidimensional potential of mean force. The method progressively learns by itself, through a feedback mechanism, which regions of a multidimensional space are worth exploring and automatically generates a set of umbrella sampling windows that is adapted to the system. The self-learning adaptive umbrella sampling method is first explained with illustrative examples based on simplified reduced model systems and then applied to two nontrivial situations: the conformational equilibrium of the pentapeptide Met-enkephalin in solution and ion permeation in the KcsA potassium channel. With this method, it is demonstrated that a significant smaller number of umbrella windows needs to be employed to characterize the free energy landscape over the most relevant regions without any loss in accuracy.