Solution nuclear magnetic resonance (NMR) experiments allow RNA dynamics to be determined in an aqueous environment. However, when a limited number of peaks are assigned, it is difficult to obtain structural information. We here show a protocol based on the combination of experimental data (Nuclear Overhauser Effect, NOE) and molecular dynamics simulations with enhanced sampling methods. This protocol allows to (a) obtain a maximum entropy ensemble compatible with NMR restraints and (b) obtain a minimal set of metastable conformations compatible with the experimental data (maximum parsimony). The method is applied to a hairpin of 29 nt from an inverted SINEB2, which is part of the SINEUP family and has been shown to enhance protein translation. A clustering procedure is introduced where the annotation of base-base interactions and glycosidic bond angles is used as a metric. By reweighting the contributions of the clusters, minimal sets of four conformations could be found which are compatible with the experimental data. A motif search on the structural database showed that some identified low-population states are present in experimental structures of other RNA transcripts. The introduced method can be applied to characterize RNA dynamics in systems where a limited amount of NMR information is available.

Conformational ensembles of an RNA hairpin using molecular dynamics and sparse NMR data / Reißer, Sabine; Zucchelli, Silvia; Gustincich, Stefano; Bussi, Giovanni. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 48:3(2020), pp. 1164-1174. [10.1093/nar/gkz1184]

Conformational ensembles of an RNA hairpin using molecular dynamics and sparse NMR data

Reißer, Sabine;Zucchelli, Silvia;Bussi, Giovanni
2020

Abstract

Solution nuclear magnetic resonance (NMR) experiments allow RNA dynamics to be determined in an aqueous environment. However, when a limited number of peaks are assigned, it is difficult to obtain structural information. We here show a protocol based on the combination of experimental data (Nuclear Overhauser Effect, NOE) and molecular dynamics simulations with enhanced sampling methods. This protocol allows to (a) obtain a maximum entropy ensemble compatible with NMR restraints and (b) obtain a minimal set of metastable conformations compatible with the experimental data (maximum parsimony). The method is applied to a hairpin of 29 nt from an inverted SINEB2, which is part of the SINEUP family and has been shown to enhance protein translation. A clustering procedure is introduced where the annotation of base-base interactions and glycosidic bond angles is used as a metric. By reweighting the contributions of the clusters, minimal sets of four conformations could be found which are compatible with the experimental data. A motif search on the structural database showed that some identified low-population states are present in experimental structures of other RNA transcripts. The introduced method can be applied to characterize RNA dynamics in systems where a limited amount of NMR information is available.
NUCLEIC ACIDS RESEARCH
48
3
1164
1174
10.1093/nar/gkz1184
Reißer, Sabine; Zucchelli, Silvia; Gustincich, Stefano; Bussi, Giovanni
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/108474
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