Coarse-grained simulations of RNA and DNA duplexes

J Phys Chem B. 2013 Jul 11;117(27):8047-60. doi: 10.1021/jp400786b. Epub 2013 Jun 26.

Abstract

Although RNAs play many cellular functions, little is known about the dynamics and thermodynamics of these molecules. In principle, all-atom molecular dynamics simulations can investigate these issues, but with current computer facilities, these simulations have been limited to small RNAs and to short times. HiRe-RNA, a recently proposed high-resolution coarse-grained RNA that captures many geometric details such as base pairing and stacking, is able to fold RNA molecules to near-native structures in a short computational time. So far, it had been applied to simple hairpins, and here we present its application to duplexes of a couple dozen nucleotides and show how with replica exchange molecular dynamics (REMD) we can easily predict the correct double helix from a completely random configuration and study the dissociation curve. To show the versatility of our model, we present an application to a double stranded DNA molecule as well. A reconstruction algorithm allows us to obtain full atom structures from the coarse-grained model. Through atomistic molecular dynamics (MD), we can compare the dynamics starting from a representative structure of a low temperature replica or from the experimental structure, and show how the two are statistically identical, highlighting the validity of a coarse-grained approach for structured RNAs and DNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing
  • DNA / chemistry*
  • Hydrogen Bonding
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • Software
  • Temperature
  • Thermodynamics

Substances

  • RNA
  • DNA