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 increase of Mg2+ affinity due to ion competition and hybridization, respectively, and predict that RNA flexibility has a site-dependent effect. This suggests a nontrivial interplay between RNA conformational entropy and divalent cation binding.

Unravelling Mg2+-RNA binding with atomistic molecular dynamics / Andre Cunha, Richard; Bussi, Giovanni. - In: RNA. - ISSN 1355-8382. - 23:5(2017), pp. 628-638. [10.1261/rna.060079.116]

Unravelling Mg2+-RNA binding with atomistic molecular dynamics

Andre Cunha, Richard;Bussi, Giovanni
2017-01-01

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 increase of Mg2+ affinity due to ion competition and hybridization, respectively, and predict that RNA flexibility has a site-dependent effect. This suggests a nontrivial interplay between RNA conformational entropy and divalent cation binding.
2017
RNA
23
5
628
638
https://arxiv.org/abs/1612.08550
Andre Cunha, Richard; Bussi, Giovanni
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/11944
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