Protein-protein interface analysis and hot spots identification for chemical Ligand design

Jing Chen, Xiaomin Ma, Yaxia Yuan, Jianfeng Pei, Luhua Lai

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Rational design for chemical compounds targeting protein-protein interactions has grown from a dream to reality after a decade of efforts. There are an increasing number of successful examples, though major challenges remain in the field. In this paper, we will first give a brief review of the available methods that can be used to analyze protein-protein interface and predict hot spots for chemical ligand design. New developments of binding sites detection, ligandability and hot spots prediction from the author's group will also be described. Pocket V.3 is an improved program for identifying hot spots in protein-protein interface using only an apo protein structure. It has been developed based on Pocket V.2 that can derive receptor-based pharmacophore model for ligand binding cavity. Given similarities and differences between the essence of pharmacophore and hot spots for guiding design of chemical compounds, not only energetic but also spatial properties of protein-protein interface are used in Pocket V.3 for dealing with protein-protein interface. In order to illustrate the capability of Pocket V.3, two datasets have been used. One is taken from ASEdb and BID having experimental alanine scanning results for testing hot spots prediction. The other is taken from the 2P2I database containing complex structures of protein-ligand binding at the original protein-protein interface for testing hot spots application in ligand design.

Original languageEnglish (US)
Pages (from-to)1192-1200
Number of pages9
JournalCurrent pharmaceutical design
Issue number8
StatePublished - 2014
Externally publishedYes


  • Binding site detection
  • Hot spots
  • Ligandability
  • Pocket V.3
  • Protein-protein interface analysis
  • Small molecular binder

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery


Dive into the research topics of 'Protein-protein interface analysis and hot spots identification for chemical Ligand design'. Together they form a unique fingerprint.

Cite this