Tuesday, 26 April 2011

A novel web-oriented peptidomimetic compound virtual screening tool.

pepMMsMIMIC is a public, web-based virtual screening platform with the aim to suggest chemical compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space which hopefully retain the ability to interact with the biological target and produce the typical biological effect.
Starting from the 3D structure of any protein-protein/peptide complex, pepMMsMIMIC design process begins by identifying the key residues that are responsible for the protein-protein recognition process. In this process, the peptide complexity is reduced and the basic pharmacophore model is defined by its critical structural features (peptide annotation points) in 3D space.
The pepMMsMIMIC paper has been accepted for publication in the NAR Web Server Issue 2011. I will post the Advance Access link in the near future.
Here the abstract:

pepMMsMIMIC is a novel web-oriented peptidomimetic compound virtual screening tool based on a multi-conformers 3D- similarity search strategy. Key to the development of pepMMsMIMIC has been the creation of a library of 17 million conformers calculated from 3.9 million commercially available chemicals collected in the MMsINC® database. Using as input the three-dimensional structure of a peptide bound to a protein, pepMMsMIMIC suggests which chemical structures are able to mimic the protein-protein recognition of this natural peptide using both pharmacophore and shape similarity techniques. We hope that the accessibility of pepMMsMIMIC will encourage medicinal chemists to de-peptidize protein-protein recognition processes of biological interest, thus increasing the potential of in silico peptidomimetic compound screening of known small molecules to expedite drug development.


  1. Very nice! next step will be the searching for inhibitors of PPI?

  2. Thanks Vladimir. You can search them with this tool: if you know the 3D structure of the interacting proteins, and the key residues, of course, you can load the 3D structure of the peptide/ protein and run the screening. The example peptide belongs to the p53 protein, whose interaction with hdm2 is a well known target. We validated the tool by using some known PPIs (nutlins).

  3. Very nice indeed! This could be combined with peptide-protein modeling. We recently developed a high-resolution peptide docking web-server (also to appear in NAR 2011 web-server issue) Rosetta FlexPepDock (http://flexpepdock.furmanlab.cs.huji.ac.il/) Your server is a natural extention for making these modeled peptides into inhibitors. Exciting.

  4. Nir, if you are interested, we can discuss a bit more about a possible "connection" between our servers... my email is matteo.floris@gmail.com

  5. sir ,i have used your server but score is very low (0.01 and 000),how could i proceed further

  6. can you send more details by email? please send me the job url. (matteo.floris@gmail.com)