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Title: Fast, clash-free RNA conformational morphing using molecular junctions

Abstract

Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groups of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elementsmore » guide large parts of the molecule along the transition to the correct final conformation.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Univ. Paris-Saclay, Palaiseau (France)
  2. Univ. of Erlangen-Nuremberg, Erlangen (Germany)
  3. Stanford Univ., Stanford, CA (United States); SLAC National Accelerator Lab., Menlo Park, CA (United States)
  4. Stanford Univ., Menlo Park, CA (United States). SLAC National Accelerator Lab.
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1368458
Grant/Contract Number:  
AC02-76SF00515
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Bioinformatics
Additional Journal Information:
Journal Volume: 33; Journal Issue: 14; Journal ID: ISSN 1367-4803
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Heliou, Amelie, Budday, Dominik, Fonseca, Rasmus, and van den Bedem, Henry. Fast, clash-free RNA conformational morphing using molecular junctions. United States: N. p., 2017. Web. doi:10.1093/bioinformatics/btx127.
Heliou, Amelie, Budday, Dominik, Fonseca, Rasmus, & van den Bedem, Henry. Fast, clash-free RNA conformational morphing using molecular junctions. United States. doi:10.1093/bioinformatics/btx127.
Heliou, Amelie, Budday, Dominik, Fonseca, Rasmus, and van den Bedem, Henry. Mon . "Fast, clash-free RNA conformational morphing using molecular junctions". United States. doi:10.1093/bioinformatics/btx127. https://www.osti.gov/servlets/purl/1368458.
@article{osti_1368458,
title = {Fast, clash-free RNA conformational morphing using molecular junctions},
author = {Heliou, Amelie and Budday, Dominik and Fonseca, Rasmus and van den Bedem, Henry},
abstractNote = {Non-coding ribonucleic acids (ncRNA) are functional RNA molecules that are not translated into protein. They are extremely dynamic, adopting diverse conformational substates, which enables them to modulate their interaction with a large number of other molecules. The flexibility of ncRNA provides a challenge for probing their complex 3D conformational landscape, both experimentally and computationally. As a result, despite their conformational diversity, ncRNAs mostly preserve their secondary structure throughout the dynamic ensemble. Here we present a kinematics-based procedure to morph an RNA molecule between conformational substates, while avoiding inter-atomic clashes. We represent an RNA as a kinematic linkage, with fixed groups of atoms as rigid bodies and rotatable bonds as degrees of freedom. Our procedure maintains RNA secondary structure by treating hydrogen bonds between base pairs as constraints. The constraints define a lower-dimensional, secondary-structure constraint manifold in conformation space, where motions are largely governed by molecular junctions of unpaired nucleotides. On a large benchmark set, we show that our morphing procedure compares favorably to peer algorithms, and can approach goal conformations to within a low all-atom RMSD by directing fewer than 1% of its atoms. Furthermore, our results suggest that molecular junctions can modulate 3D structural rearrangements, while secondary structure elements guide large parts of the molecule along the transition to the correct final conformation.},
doi = {10.1093/bioinformatics/btx127},
journal = {Bioinformatics},
number = 14,
volume = 33,
place = {United States},
year = {Mon Mar 13 00:00:00 EDT 2017},
month = {Mon Mar 13 00:00:00 EDT 2017}
}

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