Binding mode analysis between membrane dipeptidase and its substrates

M. Kim, J. Kim, E. Jung, K. Choi, J. M. Shin, S. K. Kang, M. K. Kim, Y. J. Choi, S. H. Choi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Membrane dipeptidase (MDP) is a membrane-bound glycoprotein involved in the hydrolysis of dipeptides, showing specific activity for dipeptides. Recent study showed that membrane dipeptidase was the receptor for a lung-targeting peptide identified by in vivo phage display and the crystal structure of the cilastatin-liganded human renal dipeptidase was determined. We performed a pharmacophore-based virtual screening and molecular docking in order to characterize MDP binding interactions with its substrates. A ligand-based pharmacophore model represented only a slight enrichment because of a lacked variety and centralization of ligand features. Molecular docking study was used to incorporate ligand conformational changes in the binding sites and the performance was much better than pharmacophore model; only 10% of compound library needed to be screened in order to detect all included active compounds. In addition, we found that one of the crystallographically observed water molecules plays an important role in the binding modes between MDP and its substrate.

Original languageEnglish
Pages (from-to)495-503
Number of pages9
JournalMolecular Simulation
Volume33
Issue number6
DOIs
Publication statusPublished - 2007 May

Keywords

  • Cilastatin
  • Docking
  • Membrane dipeptidase (MDP)
  • Pharmacophore
  • Virtual screening

ASJC Scopus subject areas

  • Chemistry(all)
  • Information Systems
  • Modelling and Simulation
  • Chemical Engineering(all)
  • Materials Science(all)
  • Condensed Matter Physics

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  • Cite this

    Kim, M., Kim, J., Jung, E., Choi, K., Shin, J. M., Kang, S. K., Kim, M. K., Choi, Y. J., & Choi, S. H. (2007). Binding mode analysis between membrane dipeptidase and its substrates. Molecular Simulation, 33(6), 495-503. https://doi.org/10.1080/08927020701236763