A combined QM/MM study of the nucleophilic addition reaction of methanethiolate and N-methylacetamide

Kyoungrim Byun, Jiali Gao

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

A combined quantum mechanical (QM) and molecular mechanical (MM) method was used to study the nucleophilic addition reaction of methanethiolate to N-methylacetamide (NMA) in the gas phase and aqueous solution. At the B3LYP/aug-cc-pVDZ//HF/6-31+G(d) level, the ion-dipole complex was found to be the global minimum on the potential energy surface in the gas phase with a binding energy of 21.2 kcal/mol. The complex has a C-S distance of 4.33 Å, and no stabilized tetrahedral intermediate was located. The computed potential of mean force in water shows that solvent effects stabilize the reactants over the tetrahedral adduct by 36.5 kcal/mol, and that the tetrahedral intermediate does not exist for the present reaction in water. The present study provides an initial step for modeling the cysteine protease hydrolysis reactions in enzymes.

Original languageEnglish (US)
Pages (from-to)50-55
Number of pages6
JournalJournal of Molecular Graphics and Modelling
Volume18
Issue number1
DOIs
StatePublished - Dec 1 2000

Keywords

  • Combined QM/MM simulations
  • Monte Carlo simulation
  • Nucleophilic addition reaction
  • Potential of mean force
  • Solvent effects

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