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Atomic Interactions and Profile of Small Molecules Disrupting Protein–Protein Interfaces: the TIMBAL Database
Author(s) -
Higueruelo Alícia P.,
Schreyer Adrian,
Bickerton G. Richard J.,
Pitt Will R.,
Groom Colin R.,
Blundell Tom L.
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2009.00889.x
Subject(s) - protein data bank (rcsb pdb) , small molecule , database , chemistry , drug discovery , protein–protein interaction , protein data bank , molecule , computational biology , protein structure , stereochemistry , biology , computer science , biochemistry , organic chemistry
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 http://www-cryst.bioc.cam.ac.uk/timbal.