A two-dimensional replica-exchange molecular dynamics method for simulating RNA folding using sparse experimental restraints

Parisa Ebrahimi; Simi Kaur; Lorenzo Baronti; Katja Petzold; Alan A Chen

doi:10.1016/j.ymeth.2019.05.001

A two-dimensional replica-exchange molecular dynamics method for simulating RNA folding using sparse experimental restraints

Methods. 2019 Jun 1:162-163:96-107. doi: 10.1016/j.ymeth.2019.05.001. Epub 2019 May 3.

Authors

Parisa Ebrahimi¹, Simi Kaur¹, Lorenzo Baronti², Katja Petzold², Alan A Chen³

Affiliations

¹ Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA.
² Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
³ Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA; The RNA Institute, University at Albany, State University of New York, Albany, NY, USA. Electronic address: [email protected].

PMID: 31059830
DOI: 10.1016/j.ymeth.2019.05.001

Abstract

We present a 2D replica exchange protocol incorporating secondary structure information to dramatically improve 3D RNA folding using molecular dynamics simulations. We show that incorporating base-pairing restraints into all-atom, explicit solvent simulations enables the accurate recapitulation of the global tertiary fold for 4 representative RNAs ranging in length from 24 to 68 nt. This method can potentially utilize base-pairing information from a wide variety of experimental inputs to predict complex RNA tertiary folds including pseudoknots, multi-loop junctions, and non-canonical interactions.

Keywords: Molecular dynamics simulations; RNA folding; RNA structure prediction; Replica-exchange.

Publication types

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

MeSH terms

Base Pairing
Computational Biology / methods*
Molecular Dynamics Simulation*
RNA Folding*
RNA, Bacterial / chemistry
RNA, Bacterial / metabolism
RNA, Viral / chemistry
RNA, Viral / metabolism
Thermodynamics

Substances

RNA, Bacterial
RNA, Viral