Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Conformational Ensembles of Noncoding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations. / Bottaro, Sandro; Bussi, Giovanni; Lindorff-Larsen, Kresten.
In: Journal of the American Chemical Society, Vol. 143, No. 22, 2021, p. 8333-8343.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 -
ID: 273587909