title: Subtle Monte Carlo Updates in Dense Molecular Systems.
abstract: Although Markov chain Monte Carlo (MC) simulation is a potentially powerful approach for exploring conformational space, it has been unable to compete with molecular dynamics (MD) in the analysis of high density structural states, such as the native state of globular proteins. Here, we introduce a kinetic algorithm, CRISP, that greatly enhances the sampling efficiency in all-atom MC simulations of dense systems. The algorithm is based on an exact analytical solution to the classic chain-closure problem, making it possible to express the interdependencies among degrees of freedom in the molecule as correlations in a multivariate Gaussian distribution. We demonstrate that our method reproduces structural variation in proteins with greater efficiency than current state-of-the-art Monte Carlo methods and has real-time simulation performance on par with molecular dynamics simulations. The presented results suggest our method as a valuable tool in the study of molecules in atomic detail, offering a potential alternative to molecular dynamics for probing long time-scale conformational transitions.
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Sandro
authors.initials: S
authors.lastname: Bottaro
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark.|Department of Astronomy and Theoretical Physics, Lund University, Lund, Sweden.
authors.forename: Wouter
authors.initials: W
authors.lastname: Boomsma
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: E Johansson
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Andreetta
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamelryck
authors.affiliation: Department of Electrical Engineering, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Ferkinghoff-Borg