Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models

Andrey Krokhotin, Nikolay Dokholyan

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Citations (Scopus)

Abstract

Computational methods can provide significant insights into RNA structure and dynamics, bridging the gap in our understanding of the relationship between structure and biological function. Simulations enrich and enhance our understanding of data derived on the bench, as well as provide feasible alternatives to costly or technically challenging experiments. Coarse-grained computational models of RNA are especially important in this regard, as they allow analysis of events occurring in timescales relevant to RNA biological function, which are inaccessible through experimental methods alone. We have developed a three-bead coarse-grained model of RNA for discrete molecular dynamics simulations. This model is efficient in de novo prediction of short RNA tertiary structure, starting from RNA primary sequences of less than 50 nucleotides. To complement this model, we have incorporated additional base-pairing constraints and have developed a bias potential reliant on data obtained from hydroxyl probing experiments that guide RNA folding to its correct state. By introducing experimentally derived constraints to our computer simulations, we are able to make reliable predictions of RNA tertiary structures up to a few hundred nucleotides. Our refined model exemplifies a valuable benefit achieved through integration of computation and experimental methods.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
PublisherAcademic Press Inc.
Pages65-89
Number of pages25
DOIs
StatePublished - Jan 1 2015

Publication series

NameMethods in Enzymology
Volume553
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Fingerprint

Computational methods
RNA
Atoms
Nucleotides
Guide RNA
RNA Folding
Molecular Dynamics Simulation
Base Pairing
Hydroxyl Radical
Computer Simulation
Computer simulation
Molecular dynamics
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Krokhotin, A., & Dokholyan, N. (2015). Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models. In Methods in Enzymology (pp. 65-89). (Methods in Enzymology; Vol. 553). Academic Press Inc.. https://doi.org/10.1016/bs.mie.2014.10.052
Krokhotin, Andrey ; Dokholyan, Nikolay. / Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models. Methods in Enzymology. Academic Press Inc., 2015. pp. 65-89 (Methods in Enzymology).
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Krokhotin, A & Dokholyan, N 2015, Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models. in Methods in Enzymology. Methods in Enzymology, vol. 553, Academic Press Inc., pp. 65-89. https://doi.org/10.1016/bs.mie.2014.10.052

Computational methods toward accurate RNA structure prediction using coarse-grained and all-atom models. / Krokhotin, Andrey; Dokholyan, Nikolay.

Methods in Enzymology. Academic Press Inc., 2015. p. 65-89 (Methods in Enzymology; Vol. 553).

Research output: Chapter in Book/Report/Conference proceedingChapter

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