A parallel implementation of the Wuchty algorithm with additional experimental filters to more thoroughly explore RNA conformational space

Jonathan W Stone; Samuel Bleckley; Sean Lavelle; Susan J Schroeder

doi:10.1371/journal.pone.0117217

A parallel implementation of the Wuchty algorithm with additional experimental filters to more thoroughly explore RNA conformational space

PLoS One. 2015 Feb 19;10(2):e0117217. doi: 10.1371/journal.pone.0117217. eCollection 2015.

Authors

Jonathan W Stone¹, Samuel Bleckley¹, Sean Lavelle¹, Susan J Schroeder¹

Affiliation

¹ Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma, United States of America; Department of Microbiology and Plant Biology, University of Oklahoma, Norman, Oklahoma, United States of America.

Abstract

We present new modifications to the Wuchty algorithm in order to better define and explore possible conformations for an RNA sequence. The new features, including parallelization, energy-independent lonely pair constraints, context-dependent chemical probing constraints, helix filters, and optional multibranch loops, provide useful tools for exploring the landscape of RNA folding. Chemical probing alone may not necessarily define a single unique structure. The helix filters and optional multibranch loops are global constraints on RNA structure that are an especially useful tool for generating models of encapsidated viral RNA for which cryoelectron microscopy or crystallography data may be available. The computations generate a combinatorially complete set of structures near a free energy minimum and thus provide data on the density and diversity of structures near the bottom of a folding funnel for an RNA sequence. The conformational landscapes for some RNA sequences may resemble a low, wide basin rather than a steep funnel that converges to a single structure.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Algorithms
Computer Simulation
Models, Molecular
RNA / chemistry*
RNA / genetics
RNA Folding
Sequence Analysis, RNA
Software

Substances

RNA

Associated data

figshare/10.6084/M9.FIGSHARE.1276050

Grants and funding

This work was supported by grants from the National Science Foundation CAREER grant no. 0844913, the Oklahoma Center for the Advancement of Science and Technology HR13-206, and the Pharmaceutical Research and Manufacturers of America Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.