title: RNA/Peptide Binding Driven by Electrostatics-Insight from Bidirectional Pulling Simulations.
abstract: RNA/protein interactions play crucial roles in controlling gene expression. They are becoming important targets for pharmaceutical applications. Due to RNA flexibility and to the strength of electrostatic interactions, standard docking methods are insufficient. We here present a computational method which allows studying the binding of RNA molecules and charged peptides with atomistic, explicit-solvent molecular dynamics. In our method, a suitable estimate of the electrostatic interaction is used as an order parameter (collective variable) which is then accelerated using bidirectional pulling simulations. Since the electrostatic interaction is only used to enhance the sampling, the approximations used to compute it do not affect the final accuracy. The method is employed to characterize the binding of TAR RNA from HIV-1 and a small cyclic peptide. Our simulation protocol allows blindly predicting the binding pocket and pose as well as the binding affinity. The method is general and could be applied to study other electrostatics-driven binding events.
authors.affiliation: SISSA/ISAS - International School for Advanced Studies, Trieste 34136, Italy.
authors.forename: Trang N
authors.initials: TN
authors.lastname: Do
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences, D-52425 Jülich, Germany and Institute for Advanced Simulation IAS-5, Computational Biomedicine, Forschungszentrum Jülich, D-52425 Jülich, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.affiliation: Department of Chemistry and Department of Biochemistry, University of Washington, Seattle, Washington 98195-1700, United States.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Varani
authors.affiliation: SISSA/ISAS - International School for Advanced Studies, Trieste 34136, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bussi