Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database

Chem Biol Drug Des. 2009 Nov;74(5):457-67. doi: 10.1111/j.1747-0285.2009.00889.x.


Growing evidence of the possibility of modulating protein-protein interactions with small molecules is opening the door to new approaches and concepts in drug discovery. In this paper, we describe the creation of TIMBAL, a hand-curated database holding an up to date collection of small molecules inhibiting multi-protein complexes. This database has been analysed and profiled in terms of molecular properties. Protein-protein modulators tend to be large lipophilic molecules with few hydrogen bond features. An analysis of TIMBAL's intersection with other structural databases, including CREDO (protein-small molecule from the PDB) and PICCOLO (protein-protein from the PDB) reveals that TIMBAL molecules tend to form mainly hydrophobic interactions with only a few hydrogen bonding contacts. With respect to potency, TIMBAL molecules are slightly less efficient than an average medicinal chemistry hit or lead. The database provides a resource that will allow further insights into the types of molecules favoured by protein interfaces and provide a background to continuing work in this area. Access at

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein*
  • Drug Design*
  • Humans
  • Hydrogen Bonding
  • Hydrophobic and Hydrophilic Interactions
  • Protein Binding
  • Proteins / chemistry*


  • Proteins