Mg2+ cations play a major role in RNA stabilization and folding, both by contributing to the ionic atmosphere, thus reducing electrostatic repulsion, and by binding directly to RNA. These direct interactions are often related to well-defined structural motifs and to biological functions [1,2]. We perform extensive atomistic molecular dynamics (MD) simulations in explicit solvent using a recently developed Mg2+ parametrization [3] in order to study the thermodynamics of the Mg2+/RNA interaction. Direct Mg2+/RNA binding is hindered by free-energy barriers largely related to Mg2+ desolvation and is not easily accessible in plain MD. We thus use an ad hoc modified variant of bias exchange metadynamics [4,5] to systematically compute the affinity of Mg2+ with all the possible binding sites in RNA, both on single nucleotides and in a duplex. Results are compared with an analysis of Mg2+ binding sites from structural databases [6], and could possibly be used to interpret and guide experimental studies of RNA folding. 1 - Draper D., Biophys. Journal, 2008. 2 - Lipfert, J., Doniach S., Das R. and Herschlag D., Annu. Rev. Biochem., 2014. 3 - Allnér O., Nilsson L. and Villa A., JCTC, 2012. 4 - Laio A. and Parrinello M., PNAS, 2002. 5 - Laio A. and Piana E., The J.l of Phys. Chem. B, 2009 6 - Zheng H., Bujnick N., NAR 2015.

Mg2+/RNA binding: Insights from atomistic molecular dynamics with enhanced sampling

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.