title: Empirical Corrections to the Amber RNA Force Field with Target Metadynamics.
abstract: The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement.
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA) , via Bonomea 265, 34136 Trieste, Italy.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gil-Ley
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA) , via Bonomea 265, 34136 Trieste, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Bottaro
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA) , via Bonomea 265, 34136 Trieste, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussi
mesh_terms: D000465:Algorithms; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D012313:RNA