QM/MM simulations indicate that Asp185 is the likely catalytic base in the enzymatic reaction of HIV-1 reverse transcriptase

Thanyada Rungrotmongkol, Adrian J. Mulholland, Supa Hannongbua*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)

Abstract

Alternative possible mechanisms of reaction in HIV-1 reverse transcriptase are studied here by QM/MM molecular dynamics umbrella sampling simulations. Two protonation states of the dTTP substrate are tested. Among three different pathways, Asp185 is the probable base for deprotonation of the 3 '-primer terminus prior to nucleotide addition on fully-deprotonated dTTP with formation of the stable final product complex of DNA(n+1) and PPi. In contrast, the reactions via dTTP or Asp186 as the base show higher energy barriers for either deprotonation or nucleotide addition.

Original languageEnglish
Pages (from-to)593-596
Number of pages4
JournalMedChemComm
Volume5
Issue number5
DOIs
Publication statusPublished - May 2014

Keywords

  • DNA-POLYMERASE
  • NUCLEOTIDYL TRANSFER
  • FREE-ENERGY
  • DYNAMICS
  • SITE
  • RNA
  • PROGRAM
  • CHARMM
  • VIRUS
  • ACID

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