Why Does RNA Collapse? The Importance of Water in a Simulation Study of Helix-Junction-Helix Systems

J Am Chem Soc. 2018 Dec 12;140(49):16948-16951. doi: 10.1021/jacs.8b11111. Epub 2018 Nov 29.

Abstract

Using computer simulations, we consider the balance of thermodynamic forces that collapse RNA. A model helix-junction-helix (HJH) construct is used to investigate the transition from an extended to a collapsed conformation. Conventional Molecular Dynamics and Milestoning Simulations are used to study the free energy profile of the process for two ion concentrations. We illustrate that HJH folds to a collapsed state with two types of counterions (Mg2+ and K+). By dissecting the free energy landscape into energetic and entropic contributions, we illustrate that the electrostatic forces between the RNA and the mobile ions do not drive the RNA to a collapsed state. Instead, entropy gains from water expulsion near the neighborhood of the RNA provide the stabilization free energy that tilt HJH into more compact structures. Further simulations of a three-helix hammerhead ribozyme show a similar behavior and support the idea of collapse due to increased gain in water entropy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Magnesium / chemistry
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Potassium / chemistry
  • RNA, Catalytic / chemistry*
  • Thermodynamics
  • Water / chemistry*

Substances

  • RNA, Catalytic
  • hammerhead ribozyme
  • Water
  • Magnesium
  • Potassium