Mechanistic insights into metal (Pd2+, Co2+, and Zn2+)-β-cyclodextrin catalyzed peptide hydrolysis: A QM/MM approach

Tingting Zhang, Xiaoxia Zhu, Rajeev Prabhakar

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In this study, mechanistic insights into the hydrolysis of an extremely stable tertiary peptide bond (Ser-Pro) in the Ser-Pro-Phe sequence by an artificial enzyme, metal (Pd2+, Co2+, or Zn 2+)-β-cyclodextrin (CD) complex, have been provided. In particular, the exact reaction mechanism, the location of CD (number of -CH 2 groups downstream from the metal center), conformation of CD (primary or secondary rim of CD facing the substrate), the number of CD (one or two), and the optimum metal ion (Pd2+, Co2+, or Zn 2+) have been suggested using a state-of-the-art hybrid quantum mechanics/molecular mechanics (QM/MM: B3LYP/Amber) approach. The QM/MM calculations suggest that the internal delivery mechanism is the most energetically feasible for the peptide hydrolysis. The inclusion of a CD ring at two CH2 groups downstream from the metal center can provide 3 × 105 times acceleration in the activity, while the replacement of Pd2+ with Co2+ enhances the rate activity another 3.7 × 104 times.

Original languageEnglish
Pages (from-to)4106-4114
Number of pages9
JournalJournal of Physical Chemistry B
Volume118
Issue number15
DOIs
StatePublished - Apr 17 2014

Fingerprint

Cyclodextrins
Peptides
peptides
hydrolysis
Hydrolysis
Metals
metals
rims
enzymes
quantum mechanics
metal ions
delivery
inclusions
methylidyne
Amber
Molecular mechanics
Quantum theory
rings
Metal ions
Conformations

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Mechanistic insights into metal (Pd2+, Co2+, and Zn2+)-β-cyclodextrin catalyzed peptide hydrolysis : A QM/MM approach. / Zhang, Tingting; Zhu, Xiaoxia; Prabhakar, Rajeev.

In: Journal of Physical Chemistry B, Vol. 118, No. 15, 17.04.2014, p. 4106-4114.

Research output: Contribution to journalArticle

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