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 V.
N1 - Funding Information:
The authors would like to thank David Shirvanyants, Jared Baisden and Josh Boyer for stimulating discussions. National Institutes of Health [R35GM122532 to K.M.W., R01GM114015, R01GM064803, R01GM123247 to N.V.D., R01GM114432 to Q.Z.]; University of North Carolina at Chapel Hill Start-up Funds [to Q.Z.]. Funding for open access charge: National Institutes of Health [R01GM064803].
Funding Information:
National Institutes of Health [R35GM122532 to K.M.W., R01GM114015, R01GM064803, R01GM123247 to N.V.D., R01GM114432 to Q.Z.]; University of North Carolina at Chapel Hill Start-up Funds [to Q.Z.]. Funding for open access charge: National Institutes of Health [R01GM064803].
Publisher Copyright:
© 2017 The Author(s).
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.
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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 -