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 language | English (US) |
|---|---|
| Pages (from-to) | 12638-12647 |
| Number of pages | 10 |
| Journal | Nucleic acids research |
| Volume | 45 |
| Issue number | 22 |
| DOIs | |
| State | Published - Dec 15 2017 |
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All Science Journal Classification (ASJC) codes
- Genetics
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Structure modeling of RNA using sparse NMR constraints. / Williams, Benfeard; Zhao, Bo; Tandon, Arpit; Ding, Feng; Weeks, Kevin M.; Zhang, Qi; Dokholyan, Nikolay V.
In: Nucleic acids research, Vol. 45, No. 22, 15.12.2017, p. 12638-12647.Research output: Contribution to journal › Article
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.
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 -