TY - JOUR

T1 - Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

AU - Bottaro, Sandro

AU - Bussi, Giovanni

AU - Lindorff-Larsen, Kresten

N1 - Funding Information: We acknowledge Drs. Harald Schwalbe, Anna Wacker, Julia E. Weigand, Andreas Schlundt, and other members of the Covid19-NMR consortium for discussions and insights. S.B. and K.L.L. acknowledge funding from the Lundbeck Foundation BRAINSTRUC structural biology initiative (R155-2015-2666). We acknowledge access to computational resources from PRACE for the COVID-RNA project (COVID19-72). We thank Matteo Cagiada for preparing the TOC graphic. Publisher Copyright: © 2021 American Chemical Society. All rights reserved.

PY - 2021

Y1 - 2021

N2 - The 5′ untranslated region (UTR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structures are not known yet. Here, we predict structure and dynamics of five RNA stem loops in the 5′-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5 ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrangements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterization of these systems, and provide putative three-dimensional models for structure-based drug design studies.

AB - The 5′ untranslated region (UTR) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is a conserved, functional and structured genomic region consisting of several RNA stem-loop elements. While the secondary structure of such elements has been determined experimentally, their three-dimensional structures are not known yet. Here, we predict structure and dynamics of five RNA stem loops in the 5′-UTR of SARS-CoV-2 by extensive atomistic molecular dynamics simulations, more than 0.5 ms of aggregate simulation time, in combination with enhanced sampling techniques. We compare simulations with available experimental data, describe the resulting conformational ensembles, and identify the presence of specific structural rearrangements in apical and internal loops that may be functionally relevant. Our atomic-detailed structural predictions reveal a rich dynamics in these RNA molecules, could help the experimental characterization of these systems, and provide putative three-dimensional models for structure-based drug design studies.

U2 - 10.1021/jacs.1c01094

DO - 10.1021/jacs.1c01094

M3 - Journal article

C2 - 34039006

AN - SCOPUS:85108020534

VL - 143

SP - 8333

EP - 8343

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 22

ER -