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Journal of Chemical Sciences

, Volume 127, Issue 10, pp 1701–1713 | Cite as

Atomistic details of the molecular recognition of DNA-RNA hybrid duplex by ribonuclease H enzyme

  • GORLE SURESH
  • U DEVA PRIYAKUMAREmail author
Article

Abstract

Bacillus halodurans (Bh) ribonuclease H (RNase H) belongs to the nucleotidyl-transferase (NT) superfamily and is a prototypical member of a large family of enzymes that use two-metal ion (Mg2+ or Mn2+) catalysis to cleave nucleic acids. Long timescale molecular dynamics simulations have been performed on the BhRNase H-DNA-RNA hybrid complex and the respective monomers to understand the recognition mechanism, conformational preorganization, active site dynamics and energetics involved in the complex formation. Several structural and energetic analyses were performed and significant structural changes are observed in enzyme and hybrid duplex during complex formation. Hybrid molecule binding to RNase H enzyme leads to conformational changes in the DNA strand. The ability of the DNA strand in the hybrid duplex to sample conformations corresponding to typical A- and B-type nucleic acids and the characteristic minor groove widthseem to be crucial for efficient binding. Sugar moieties in certain positions interacting with the protein structure undergo notable conformational transitions. The water coordination and arrangement around the metal ions in active site region are quite stable, suggesting their important role in enzymatic catalysis. Details of key interactions found at the interface of enzyme-nucleic acid complex that are responsible for its stability are discussed.

Graphical Abstract

Molecular dynamics simulation results have shown that the DNA nucleotides of DNA-RNA hybrid that are interacting with ribonuclease H enzyme show interesting conformational changes upon binding.

Keywords

HIV-1 reverse transcriptase MD simulations ribonuclease H activity retroviral therapy conformational transition protein-nucleic acid interactions. 

Notes

Acknowledgements

We thank AICTE, and Department of Atomic Energy-BRNS (37(2)/14/05/2015/BRNS/20046) for financial assistance. GS thanks Council of Scientific and Industrial Research (CSIR), India for senior research fellowship.

Supplementary material

12039_2015_942_MOESM1_ESM.docx (1.8 mb)
(DOCX 1.82 MB)

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Copyright information

© Indian Academy of Sciences 2015

Authors and Affiliations

  1. 1.Center for Computational Natural Sciences and BioinformaticsInternational Institute of Information TechnologyHyderabadIndia

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