title: Characterization of the three-dimensional free energy manifold for the uracil ribonucleoside from asynchronous replica exchange simulations.
abstract: Replica exchange molecular dynamics has emerged as a powerful tool for efficiently sampling free energy landscapes for conformational and chemical transitions. However, daunting challenges remain in efficiently getting such simulations to scale to the very large number of replicas required to address problems in state spaces beyond two dimensions. The development of enabling technology to carry out such simulations is in its infancy, and thus it remains an open question as to which applications demand extension into higher dimensions. In the present work, we explore this problem space by applying asynchronous Hamiltonian replica exchange molecular dynamics with a combined quantum mechanical/molecular mechanical potential to explore the conformational space for a simple ribonucleoside. This is done using a newly developed software framework capable of executing >3,000 replicas with only enough resources to run 2,000 simultaneously. This may not be possible with traditional synchronous replica exchange approaches. Our results demonstrate 1.) the necessity of high dimensional sampling simulations for biological systems, even as simple as a single ribonucleoside, and 2.) the utility of asynchronous exchange protocols in managing simultaneous resource requirements expected in high dimensional sampling simulations. It is expected that more complicated systems will only increase in computational demand and complexity, and thus the reported asynchronous approach may be increasingly beneficial in order to make such applications available to a broad range of computational scientists.
authors.affiliation: Center for Integrative Proteomics Research BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854-8076 United States.|Department of Chemistry, University of Minnesota , Minneapolis, Minnesota 55455-0431, United States.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Radak
authors.affiliation: Department of Electrical and Computer Engineering, Rutgers University , Piscataway, New Jersey 08854-8087, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Romanus
authors.affiliation: Center for Integrative Proteomics Research BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854-8076 United States.
authors.forename: Tai-Sung
authors.initials: TS
authors.lastname: Lee
authors.affiliation: Center for Integrative Proteomics Research BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854-8076 United States.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center for Integrative Proteomics Research BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854-8076 United States.|Department of Chemistry, University of Minnesota , Minneapolis, Minnesota 55455-0431, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Electrical and Computer Engineering, Rutgers University , Piscataway, New Jersey 08854-8087, United States.
authors.forename: Antons
authors.initials: A
authors.lastname: Treikalis
authors.affiliation: Department of Electrical and Computer Engineering, Rutgers University , Piscataway, New Jersey 08854-8087, United States.
authors.forename: Vivekanandan
authors.initials: V
authors.lastname: Balasubramanian
authors.affiliation: Department of Electrical and Computer Engineering, Rutgers University , Piscataway, New Jersey 08854-8087, United States.
authors.forename: Shantenu
authors.initials: S
authors.lastname: Jha
authors.affiliation: Center for Integrative Proteomics Research BioMaPS Institute and Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854-8076 United States.
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
mesh_terms: D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory; D012263:Ribonucleosides / Q000737:chemistry*; D014498:Uracil / Q000737:chemistry*
chemical_list: D012263:Ribonucleosides; D014498:Uracil