Enhanced sampling of multidimensional free-energylandscapes using adaptive biasing forces

We propose an adaptive biasing algorithm aimed at enhancing the sampling of multimodalmeasures by Langevin dynamics. The underlying idea consists in generalizing the standardadaptive biasing force method commonly used in conjunction with molecular dynamics to handle in amore effective fashion multidimensional reaction coordinates. The proposed approach is anticipatedto be particularly useful for reaction coordinates, the components of which are weakly coupled, asilluminated in a mathematical analysis of the long-time convergence of the algorithm. The strengthas well as the intrinsic limitation of the method are discussed and illustrated in two realistic testcases.