A two-dimensional replica-exchange molecular dynamics method for simulating RNA folding using sparse experimental restraints

Ebrahimi, Parisa; Kaur, Simi; Baronti, Lorenzo; Petzold, Katja; Chen, Alan

doi:10.1016/j.ymeth.2019.05.001

Cited by 13 publications

(12 citation statements)

References 253 publications

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“… 11 While several fragment-based tools exist to perform such a task, 23 , 24 we here adapt an MD-based procedure. 25 Similar secondary structure restraining approaches have been employed in all-atom RNA folding simulations 26 , 27 and to study internal loop dynamics. 28 These initial structures are subject to extensive MD sampling, amounting to more than 0.5 ms of aggregate simulation time.…”

Section: Introductionmentioning

confidence: 99%

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

2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

2021

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“…We resolvate and minimise the RNA structures obtained from pulling as described above. We use partial tempering to enhance sampling in regions with unknown secondary structure ( Bussi, 2014; Ebrahimi et al, 2019 ). One reference replica exchanges via the Metropolis-Hastings algorithm with parallel simulations that are conducted with a modified Hamiltonian.…”

Section: Methodsmentioning

confidence: 99%

“…We resolvate and minimise the RNA structures obtained from pulling as described above. We use partial tempering to enhance sampling in regions with unknown secondary structure [66,26].…”

Section: Partial Temperingmentioning

confidence: 99%

“…While several fragment-based tools exist to perform such task [23,24], we here adapt an MD-based procedure [25]. Similar secondary structure restraining approaches have been employed in allatom RNA folding simulations [26,27] and to study internal loop dynamics [28]. These initial structures are subject to extensive MD sampling, amounting to more than 0.5ms of aggregate simulation time.…”

Section: Introductionmentioning

confidence: 99%

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Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

Bottaro

Bussi

Lindorff‐Larsen

2020

Preprint

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The 5’ untranslated region (UTR) of the 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 structure is 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 0.5ms 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 characterisation of these systems, and provide putative three-dimensional models for structure-based drug design studies.

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“…Two recent works used restraints based on the secondary structure obtained from either NMR [26] or chemical probing [2] data, employing a twodimensional replica-exchange method [27]. Here, replicas in which the experimental information is used to enforce known base pairings are coupled with unbiased replicas.…”

Section: Integrating Experimental Data and Simulations To Improve Ens...mentioning

confidence: 99%

Combining simulations and experiments to investigate RNA dynamics

Bernetti,

Bussi

2022

Preprint

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Conformational dynamics is crucial for ribonucleic acid (RNA) function. Techniques such as nuclear magnetic resonance, cryo-electron microscopy, small-and wide-angle X-ray scattering, chemical probing, or even thermal denaturation experiments probe RNA dynamics at different time and space resolutions. Their combination with accurate atomistic molecular dynamics (MD) simulations paves the way for quantitative and detailed studies of RNA dynamics. First, experiments provide a quantitative validation tool for MD simulations. Second, available data can be used to refine simulated structural ensembles to match experiments. Finally, comparison with experiments allows for improving MD force fields that are transferable to new systems for which data is not available. Here we review the recent literature and provide our perspective on this field.

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A two-dimensional replica-exchange molecular dynamics method for simulating RNA folding using sparse experimental restraints

Cited by 13 publications

References 253 publications

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

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

Conformational Ensembles of Non-Coding Elements in the SARS-CoV-2 Genome from Molecular Dynamics Simulations

Combining simulations and experiments to investigate RNA dynamics

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