title: Robust Estimation of Diffusion-Optimized Ensembles for Enhanced Sampling.
abstract: The multicanonical, or flat-histogram, method is a common technique to improve the sampling efficiency of molecular simulations. The idea is that free-energy barriers in a simulation can be removed by simulating from a distribution where all values of a reaction coordinate are equally likely, and subsequently reweight the obtained statistics to recover the Boltzmann distribution at the temperature of interest. While this method has been successful in practice, the choice of a flat distribution is not necessarily optimal. Recently, it was proposed that additional performance gains could be obtained by taking the position-dependent diffusion coefficient into account, thus placing greater emphasis on regions diffusing slowly. Although some promising examples of applications of this approach exist, the practical usefulness of the method has been hindered by the difficulty in obtaining sufficiently accurate estimates of the diffusion coefficient. Here, we present a simple, yet robust solution to this problem. Compared to current state-of-the-art procedures, the new estimation method requires an order of magnitude fewer data to obtain reliable estimates, thus broadening the potential scope in which this technique can be applied in practice.
authors.affiliation: Niels Bohr Institute, University of Copenhagen , Blegdamsvej 17, 2100 Copenhagen, Denmark.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tian
authors.affiliation: Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University , Sölvegatan 14A, SE-223 62 Lund, Sweden.
authors.forename: Sigurdur Æ
authors.initials: SÆ
authors.lastname: Jónsson
authors.affiliation: Department of Systems Biology, DTU, Søltofts Plads, 221 DK-2800, Kgs. Lyngby, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Ferkinghoff-Borg
authors.affiliation: Astbury Center for Structural Molecular Biology, University of Leeds , Leeds LS2 9JT, United Kingdom.
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Krivov
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen , Ole Maaløes Vej 5 DK-2200 Copenhagen N, Denmark.
authors.forename: Kresten
authors.initials: K
authors.lastname: Lindorff-Larsen
authors.affiliation: Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University , Sölvegatan 14A, SE-223 62 Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Irbäck
authors.affiliation: Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen , Ole Maaløes Vej 5 DK-2200 Copenhagen N, Denmark.
authors.forename: Wouter
authors.initials: W
authors.lastname: Boomsma