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


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


Aug 1, 1965·Journal of Molecular Biology·C R Cantor, I Tinoco
Jan 1, 1995·Methods in Enzymology·Martin J Serra, D H Turner
May 18, 1999·Journal of Molecular Biology·David H MathewsD H Turner
Jul 25, 2000·Journal of Molecular Biology·P Auffinger, Eric Westhof
Jun 8, 2001·Biochemistry·J M DiamondDavid H Mathews
Jul 18, 2001·Journal of the American Chemical Society·X ChenD H Turner
Jul 12, 2002·Nature·Gregory J Hannon
Dec 4, 2003·Biophysical Journal·Joanna SarzynskaTadeusz Kulinski
Oct 6, 2005·Biochemistry·Ilyas Yildirim, Douglas H Turner
Mar 7, 2006·Nature Reviews. Drug Discovery·Eugene W M NgAnthony P Adamis
Jan 6, 2010·RNA·Justin P SheehyBrent M Znosko
Feb 18, 2010·Biophysical Journal·Nan-Jie Deng, Piotr Cieplak
Mar 2, 2010·Nature Methods·Rhiju DasDavid Baker
Nov 26, 2011·Journal of Chemical Theory and Computation·Keith Van NostrandDavid H Mathews
Dec 7, 2011·Proceedings of the National Academy of Sciences of the United States of America·Parin SripakdeevongRhiju Das
Nov 1, 2012·Journal of Chemical Theory and Computation·Aleksandar SpasicDavid H Mathews
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Oct 11, 2013·Biochemistry·Zexiang Chen, Brent M Znosko
Dec 27, 2013·Nucleic Acids Research·Elzbieta KierzekRyszard Kierzek
Nov 5, 2014·Cell Research·Boxuan Simen Zhao, Chuan He
Jan 23, 2015·Journal of the American Chemical Society·Caroline RoostEric T Kool
Jul 1, 2007·Journal of Chemical Theory and Computation·Nan-Jie Deng, Piotr Cieplak


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
Computational Molecular Biology
Base Pairing
Clinical Trials

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Computational Methods for Protein Structures

Computational methods employing machine learning algorithms are powerful tools that can be used to predict the effect of mutations on protein structure. This is important in neurodegenerative disorders, where some mutations can cause the formation of toxic protein aggregations. This feed follows the latests insights into the relationships between mutation and protein structure leading to better understanding of disease.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.