title: Free energy surface of an intrinsically disordered protein: comparison between temperature replica exchange molecular dynamics and bias-exchange metadynamics.
abstract: Intrinsically disordered proteins (IDPs), which are expected to be largely unstructured under physiological conditions, make up a large fraction of eukaryotic proteins. Molecular dynamics simulations have been utilized to probe structural characteristics of these proteins, which are not always easily accessible to experiments. However, exploration of the conformational space by brute force molecular dynamics simulations is often limited by short time scales. Present literature provides a number of enhanced sampling methods to explore protein conformational space in molecular simulations more efficiently. In this work, we present a comparison of two enhanced sampling methods: temperature replica exchange molecular dynamics and bias exchange metadynamics. By investigating both the free energy landscape as a function of pertinent order parameters and the per-residue secondary structures of an IDP, namely, human islet amyloid polypeptide, we found that the two methods yield similar results as expected. We also highlight the practical difference between the two methods by describing the path that we followed to obtain both sets of data.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors.forename: Gül H
authors.initials: GH
authors.lastname: Zerze
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors.forename: Cayla M
authors.initials: CM
authors.lastname: Miller
authors.affiliation: Institute of Computational and Molecular Science, Department of Chemistry, Temple University , Philadelphia, Pennsylvania 19122, United States.
authors.forename: Daniele
authors.initials: D
authors.lastname: Granata
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University , Bethlehem, Pennsylvania 18015, United States.
authors.forename: Jeetain
authors.initials: J
authors.lastname: Mittal
mesh_terms: D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D013696:Temperature
chemical_list: D058228:Islet Amyloid Polypeptide