title: Enhanced Conformational Sampling Using Replica Exchange with  Collective-Variable Tempering.
abstract: The computational study of conformational transitions in RNA and proteins with atomistic molecular dynamics often requires suitable enhanced sampling techniques. We here introduce a novel method where concurrent metadynamics are integrated in a Hamiltonian replica-exchange scheme. The ladder of replicas is built with different strengths of the bias potential exploiting the tunability of well-tempered metadynamics. Using this method, free-energy barriers of individual collective variables are significantly reduced compared with simple force-field scaling. The introduced methodology is flexible and allows adaptive bias potentials to be self-consistently constructed for a large number of simple collective variables, such as distances and dihedral angles. The method is tested on alanine dipeptide and applied to the difficult problem of conformational sampling in a tetranucleotide.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gil-Ley
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussi
mesh_terms: D000409:Alanine / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D012313:RNA / Q000737:chemistry*
chemical_list: D004151:Dipeptides; D012313:RNA; D000409:Alanine
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