Electrostatic interactions in the hairpin ribozyme account for the majority of the rate acceleration without chemical participation by nucleobases

RNA. 2008 Aug;14(8):1501-7. doi: 10.1261/rna.863108. Epub 2008 Jun 19.

Abstract

Molecular dynamics simulations using a combined quantum mechanical/molecular mechanical potential are used to determine the two-dimensional free energy profiles for the mechanism of RNA transphosphorylation in solution and catalyzed by the hairpin ribozyme. A mechanism is explored whereby the reaction proceeds without explicit chemical participation by conserved nucleobases in the active site. The ribozyme lowers the overall free energy barrier by up to 16 kcal/mol, accounting for the majority of the observed rate enhancement. The barrier reduction in this mechanism is achieved mainly by the electrostatic environment provided by the ribozyme without recruitment of active site nucleobases as acid or base catalysts. The results establish a baseline mechanism that invokes only the solvation and specific hydrogen-bonding interactions present in the ribozyme active site and provide a departure point for the exploration of alternate mechanisms where nucleobases play an active chemical role.

Publication types

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

MeSH terms

  • Animals
  • Computer Simulation
  • Models, Chemical
  • Nucleic Acid Conformation
  • Phosphorylation
  • RNA / metabolism
  • RNA, Catalytic / chemistry*
  • Static Electricity
  • Structure-Activity Relationship
  • Thermodynamics

Substances

  • RNA, Catalytic
  • hairpin ribozyme
  • RNA