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

Kwangho Nam, Jiali Gao, Darrin York

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1501-1507
Number of pages7
JournalRNA
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

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Catalytic RNA
Static Electricity
Catalytic Domain
Molecular Dynamics Simulation
Hydrogen Bonding
RNA
Acids
hairpin ribozyme

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Keywords

  • Electrostatic interactions
  • Hairpin ribozyme
  • Ribozyme catalysis

Cite this

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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.",
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Electrostatic interactions in the hairpin ribozyme account for the majority of the rate acceleration without chemical participation by nucleobases. / Nam, Kwangho; Gao, Jiali; York, Darrin.

In: RNA, Vol. 14, No. 8, 01.08.2008, p. 1501-1507.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Electrostatic interactions in the hairpin ribozyme account for the majority of the rate acceleration without chemical participation by nucleobases

AU - Nam, Kwangho

AU - Gao, Jiali

AU - York, Darrin

PY - 2008/8/1

Y1 - 2008/8/1

N2 - 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.

AB - 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.

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