Structure modeling of RNA using sparse NMR constraints
| Autor: | Feng Ding, Qi Zhang, Bo Zhao, Arpit Tandon, Kevin M. Weeks, Nikolay V. Dokholyan, Benfeard Williams |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Distance constraints Base pair Structure (category theory) Computational biology Biology 010402 general chemistry 01 natural sciences Molecular conformation RNA Motifs 03 medical and health sciences Molecular dynamics Genetics Animals Humans Nucleotide Motifs Nucleic acid structure Base Pairing Nuclear Magnetic Resonance Biomolecular Telomerase Computational Biology RNA 0104 chemical sciences 030104 developmental biology Nucleic Acid Conformation Software |
| Zdroj: | Nucleic Acids Research |
| DOI: | 10.17615/gp3h-p817 |
| Popis: | 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 structure modeling and will facilitate analysis of diverse, newly discovered functional RNAs. |
| Databáze: | OpenAIRE |
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