Unraveling Mg²⁺-RNA binding with atomistic molecular dynamics.

ABSTRACT: Interaction with divalent cations is of paramount importance for RNA structural stability and function. We report here a detailed molecular dynamics study of all the possible binding sites for Mg²⁺ on an RNA duplex, including both direct (inner sphere) and indirect (outer sphere) binding. In order to tackle sampling issues, we develop a modified version of bias-exchange metadynamics, which allows us to simultaneously compute affinities with previously unreported statistical accuracy. Results correctly reproduce trends observed in crystallographic databases. Based on this, we simulate a carefully chosen set of models that allows us to quantify the effects of competition with monovalent cations, RNA flexibility, and RNA hybridization. Our simulations reproduce the decrease and inc

SUBMITTER: Cunha RA 

PROVIDER: S-EPMC5393174 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature