title: Hamiltonian replica exchange combined with elastic network analysis to enhance global domain motions in atomistic molecular dynamics simulations.
abstract: Coarse-grained elastic network models (ENM) of proteins offer a low-resolution representation of protein dynamics and directions of global mobility. A Hamiltonian-replica exchange molecular dynamics (H-REMD) approach has been developed that combines information extracted from an ENM analysis with atomistic explicit solvent MD simulations. Based on a set of centers representing rigid segments (centroids) of a protein, a distance-dependent biasing potential is constructed by means of an ENM analysis to promote and guide centroid/domain rearrangements. The biasing potentials are added with different magnitude to the force field description of the MD simulation along the replicas with one reference replica under the control of the original force field. The magnitude and the form of the biasing potentials are adapted during the simulation based on the average sampled conformation to reach a near constant biasing in each replica after equilibration. This allows for canonical sampling of conformational states in each replica. The application of the methodology to a two-domain segment of the glycoprotein 130 and to the protein cyanovirin-N indicates significantly enhanced global domain motions and improved conformational sampling compared with conventional MD simulations.
authors.affiliation: Physik-Department T38, Technische Universität München, 85748, Garching, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Ostermeir
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry*; D050822:Cytokine Receptor gp130 / Q000737:chemistry*; D030562:Databases, Protein; D004548:Elasticity; D006801:Humans; D007700:Kinetics; D055641:Mathematical Concepts; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046937:Nostoc / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D012997:Solvents / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; C494199:IL6ST protein, human; D010446:Peptide Fragments; D012997:Solvents; D050822:Cytokine Receptor gp130; C107733:cyanovirin N
keywords: accelerated sampling; conformational sampling; force field calculation; global protein dynamics; molecular simulations