Blind tests of RNA nearest-neighbor energy prediction

Proceedings of the National Academy of Sciences of the United States of America
Fang-Chieh ChouRhiju Das

Abstract

The predictive modeling and design of biologically active RNA molecules requires understanding the energetic balance among their basic components. Rapid developments in computer simulation promise increasingly accurate recovery of RNA's nearest-neighbor (NN) free-energy parameters, but these methods have not been tested in predictive trials or on nonstandard nucleotides. Here, we present, to our knowledge, the first such tests through a RECCES-Rosetta (reweighting of energy-function collection with conformational ensemble sampling in Rosetta) framework that rigorously models conformational entropy, predicts previously unmeasured NN parameters, and estimates these values' systematic uncertainties. RECCES-Rosetta recovers the 10 NN parameters for Watson-Crick stacked base pairs and 32 single-nucleotide dangling-end parameters with unprecedented accuracies: rmsd of 0.28 kcal/mol and 0.41 kcal/mol, respectively. For set-aside test sets, RECCES-Rosetta gives rmsd values of 0.32 kcal/mol on eight stacked pairs involving G-U wobble pairs and 0.99 kcal/mol on seven stacked pairs involving nonstandard isocytidine-isoguanosine pairs. To more rigorously assess RECCES-Rosetta, we carried out four blind predictions for stacked pairs involvi...Continue Reading

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Citations

Apr 22, 2017·Journal of Chemical Theory and Computation·Rebecca F AlfordJeffrey J Gray
Oct 27, 2018·Nucleic Acids Research·Daniel J WrightBrent M Znosko
Aug 19, 2020·Nucleic Acids Research·Melissa C HopfingerBrent M Znosko
May 29, 2018·Science Advances·Andrew WatkinsRhiju Das
Aug 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Joseph D YesselmanRhiju Das
Jun 3, 2020·Nature Methods·Julia Koehler LemanRichard Bonneau

Related Concepts

DNA Sequence
DNA Conformation
Nucleotides
RNA
Thermodynamics
Entropy
Computational Molecular Biology
Base Pairing
Classification
Clinical Trials

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