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 journalArticlepeer-review

2 Citations (Scopus)


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
Issue number6
Publication statusPublished - 2007 May

Bibliographical note

Funding Information:
This work was supported by a grant (Code: 20050401034696) from BioGreen 21 Program, Rural Development Administration, Republic of Korea. We thank Accelrys Korea for the support of modeling software.


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

ASJC Scopus subject areas

  • General Chemistry
  • Information Systems
  • Modelling and Simulation
  • General Chemical Engineering
  • General Materials Science
  • Condensed Matter Physics


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