Elucidating the Relation between Internal Motions and Dihedral Angles in an RNA Hairpin Using Molecular Dynamics

Juneja, Alok; Villa, Alessandra; Nilsson, Lennart

doi:10.1021/ct500203m

Cited by 12 publications

(9 citation statements)

References 49 publications

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“…A related work compared NMR and MD, with 100 ns MD simulation using the CHARMM36 force field characterizing the internal motions of the apical RNA stem of the human hepatitis B virus . Again, the NMR relaxation rates calculated directly from the trajectory agreed well with experiments.…”

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 80%

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

et al. 2018

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With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA–ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field.

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Section: Simulations Of Specific Rna Systemsmentioning

confidence: 80%

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

et al. 2018

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“…The high level of conformational sampling in this study was achieved using the REMD algorithm . The REMD method has been widely used in the computational study of protein folding and also the analogous process of RNA folding. − REMD consists of M noninteracting copies (or, replicas) of the original system in the canonical ensemble at M different temperatures T m ( m = 0, ..., M – 1). The replicas are arranged so that there is always one replica at each temperature.…”

Section: Methodsmentioning

confidence: 99%

Structure, Dynamics, and Function of the Hammerhead Ribozyme in Bulk Water and at a Clay Mineral Surface from Replica Exchange Molecular Dynamics

et al. 2015

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Compared with proteins, the relationship between structure, dynamics, and function of RNA enzymes (known as ribozymes) is far less well understood, despite the fact that ribozymes are found in many organisms and are often conceived as "molecular fossils" of the first self-replicating molecules to have arisen on Earth. To investigate how ribozymal function is governed by structure and dynamics, we study the full hammerhead ribozyme in bulk water and in an aqueous clay mineral environment by computer simulation using replica-exchange molecular dynamics. Through extensive sampling of the major conformational states of the hammerhead ribozyme, we are able to show that the hammerhead manifests a free-energy landscape reminiscent of that which is well known in proteins, exhibiting a "funnel" topology that guides the ribozyme into its globally most stable conformation. The active-site geometry is found to be closely correlated to the tertiary structure of the ribozyme, thereby reconciling conflicts between previously proposed mechanisms for the self-scission of the hammerhead. The conformational analysis also accounts for the differences reported experimentally in the catalytic activity of the hammerhead ribozyme, which is reduced when interacting with clay minerals as compared with bulk water.

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“…The helical regions in these systems in particular are expected to be stable over long‐timescales although there are still some reports of ‘ladders’ forming with the AMBER force field. Rapid dynamics (ps–ns) of folded RNAs, which are relevant for NMR relaxation and for ribozyme catalysis in multiscale QM/MM studies, tertiary motifs that can form without Mg 2+ (i.e., kissing‐loops, some psuedoknots) and are stable and well behaved, can be studied. Given the lack of an universally agreed upon model that accurately captures Mg 2+ ion–RNA interactions as has been discussed above, motifs that are strongly ion‐dependent (i.e., kink‐turns, quadruplexes) should be avoided.…”

Section: Resultsmentioning

confidence: 99%

Advances in RNA molecular dynamics: a simulator's guide to RNA force fields

2016

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Molecular simulations have become an essential tool for biochemical research. When they work properly, they are able to provide invaluable interpretations of experimental results and ultimately provide novel, experimentally testable predictions. Unfortunately, not all simulation models are created equal, and with inaccurate models it becomes unclear what is a bona fide prediction versus a simulation artifact. RNA models are still in their infancy compared to the many robust protein models that are widely in use, and for that reason the number of RNA force field revisions in recent years has been rapidly increasing. As there is no universally accepted 'best' RNA force field at the current time, RNA simulators must decide which one is most suited to their purposes, cognizant of its essential assumptions and their inherent strengths and weaknesses. Hopefully, armed with a better understanding of what goes inside the simulation 'black box,' RNA biochemists can devise novel experiments and provide crucial thermodynamic and structural data that will guide the development and testing of improved RNA models. WIREs RNA 2017, 8:e1396. doi: 10.1002/wrna.1396 For further resources related to this article, please visit the WIREs website.

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Elucidating the Relation between Internal Motions and Dihedral Angles in an RNA Hairpin Using Molecular Dynamics

Cited by 12 publications

References 49 publications

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

Structure, Dynamics, and Function of the Hammerhead Ribozyme in Bulk Water and at a Clay Mineral Surface from Replica Exchange Molecular Dynamics

Advances in RNA molecular dynamics: a simulator's guide to RNA force fields

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