Structure modeling of RNA using sparse NMR constraints

Benfeard Williams, Bo Zhao, Arpit Tandon, Feng Ding, Kevin M. Weeks, Qi Zhang, Nikolay Dokholyan

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

RNAs fold into distinct molecular conformations that are often essential for their functions. Accurate structure modeling of complex RNA motifs, including ubiquitous non-canonical base pairs and pseudoknots, remains a challenge. Here, we present an NMR-guided all-atom discrete molecular dynamics (DMD) platform, iFoldNMR, for rapid and accurate structure modeling of complex RNAs. We show that sparse distance constraints from imino resonances, which can be readily obtained from routine NMR experiments and easier to compile than laborious assignments of non-solvent-exchangeable protons, are sufficient to direct a DMD search for low-energy RNA conformers. Benchmarking on a set of RNAs with complex folds spanning up to 56 nucleotides in length yields structural models that recapitulate experimentally determined structures with all-heavy atom RMSDs ranging from 2.4 to 6.5 Å. This platform represents an efficient approach for high-throughput RNA structuremodeling and will facilitate analysis of diverse, newly discovered functional RNAs.

Original languageEnglish (US)
Pages (from-to)12638-12647
Number of pages10
JournalNucleic acids research
Volume45
Issue number22
DOIs
StatePublished - Dec 15 2017

Fingerprint

RNA
Molecular Dynamics Simulation
Molecular Conformation
Benchmarking
Nucleotide Motifs
Structural Models
Base Pairing
Protons
Nucleotides

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Williams, B., Zhao, B., Tandon, A., Ding, F., Weeks, K. M., Zhang, Q., & Dokholyan, N. (2017). Structure modeling of RNA using sparse NMR constraints. Nucleic acids research, 45(22), 12638-12647. https://doi.org/10.1093/nar/gkx1058
Williams, Benfeard ; Zhao, Bo ; Tandon, Arpit ; Ding, Feng ; Weeks, Kevin M. ; Zhang, Qi ; Dokholyan, Nikolay. / Structure modeling of RNA using sparse NMR constraints. In: Nucleic acids research. 2017 ; Vol. 45, No. 22. pp. 12638-12647.
@article{f8fba0e8355c4fc1a068698aacacc35c,
title = "Structure modeling of RNA using sparse NMR constraints",
abstract = "RNAs fold into distinct molecular conformations that are often essential for their functions. Accurate structure modeling of complex RNA motifs, including ubiquitous non-canonical base pairs and pseudoknots, remains a challenge. Here, we present an NMR-guided all-atom discrete molecular dynamics (DMD) platform, iFoldNMR, for rapid and accurate structure modeling of complex RNAs. We show that sparse distance constraints from imino resonances, which can be readily obtained from routine NMR experiments and easier to compile than laborious assignments of non-solvent-exchangeable protons, are sufficient to direct a DMD search for low-energy RNA conformers. Benchmarking on a set of RNAs with complex folds spanning up to 56 nucleotides in length yields structural models that recapitulate experimentally determined structures with all-heavy atom RMSDs ranging from 2.4 to 6.5 {\AA}. This platform represents an efficient approach for high-throughput RNA structuremodeling and will facilitate analysis of diverse, newly discovered functional RNAs.",
author = "Benfeard Williams and Bo Zhao and Arpit Tandon and Feng Ding and Weeks, {Kevin M.} and Qi Zhang and Nikolay Dokholyan",
year = "2017",
month = "12",
day = "15",
doi = "10.1093/nar/gkx1058",
language = "English (US)",
volume = "45",
pages = "12638--12647",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "22",

}

Williams, B, Zhao, B, Tandon, A, Ding, F, Weeks, KM, Zhang, Q & Dokholyan, N 2017, 'Structure modeling of RNA using sparse NMR constraints', Nucleic acids research, vol. 45, no. 22, pp. 12638-12647. https://doi.org/10.1093/nar/gkx1058

Structure modeling of RNA using sparse NMR constraints. / Williams, Benfeard; Zhao, Bo; Tandon, Arpit; Ding, Feng; Weeks, Kevin M.; Zhang, Qi; Dokholyan, Nikolay.

In: Nucleic acids research, Vol. 45, No. 22, 15.12.2017, p. 12638-12647.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structure modeling of RNA using sparse NMR constraints

AU - Williams, Benfeard

AU - Zhao, Bo

AU - Tandon, Arpit

AU - Ding, Feng

AU - Weeks, Kevin M.

AU - Zhang, Qi

AU - Dokholyan, Nikolay

PY - 2017/12/15

Y1 - 2017/12/15

N2 - RNAs fold into distinct molecular conformations that are often essential for their functions. Accurate structure modeling of complex RNA motifs, including ubiquitous non-canonical base pairs and pseudoknots, remains a challenge. Here, we present an NMR-guided all-atom discrete molecular dynamics (DMD) platform, iFoldNMR, for rapid and accurate structure modeling of complex RNAs. We show that sparse distance constraints from imino resonances, which can be readily obtained from routine NMR experiments and easier to compile than laborious assignments of non-solvent-exchangeable protons, are sufficient to direct a DMD search for low-energy RNA conformers. Benchmarking on a set of RNAs with complex folds spanning up to 56 nucleotides in length yields structural models that recapitulate experimentally determined structures with all-heavy atom RMSDs ranging from 2.4 to 6.5 Å. This platform represents an efficient approach for high-throughput RNA structuremodeling and will facilitate analysis of diverse, newly discovered functional RNAs.

AB - RNAs fold into distinct molecular conformations that are often essential for their functions. Accurate structure modeling of complex RNA motifs, including ubiquitous non-canonical base pairs and pseudoknots, remains a challenge. Here, we present an NMR-guided all-atom discrete molecular dynamics (DMD) platform, iFoldNMR, for rapid and accurate structure modeling of complex RNAs. We show that sparse distance constraints from imino resonances, which can be readily obtained from routine NMR experiments and easier to compile than laborious assignments of non-solvent-exchangeable protons, are sufficient to direct a DMD search for low-energy RNA conformers. Benchmarking on a set of RNAs with complex folds spanning up to 56 nucleotides in length yields structural models that recapitulate experimentally determined structures with all-heavy atom RMSDs ranging from 2.4 to 6.5 Å. This platform represents an efficient approach for high-throughput RNA structuremodeling and will facilitate analysis of diverse, newly discovered functional RNAs.

UR - http://www.scopus.com/inward/record.url?scp=85040629246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040629246&partnerID=8YFLogxK

U2 - 10.1093/nar/gkx1058

DO - 10.1093/nar/gkx1058

M3 - Article

C2 - 29165648

AN - SCOPUS:85040629246

VL - 45

SP - 12638

EP - 12647

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 22

ER -

Williams B, Zhao B, Tandon A, Ding F, Weeks KM, Zhang Q et al. Structure modeling of RNA using sparse NMR constraints. Nucleic acids research. 2017 Dec 15;45(22):12638-12647. https://doi.org/10.1093/nar/gkx1058