title: Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Cambridge, UK. alicia@cryst.bioc.cam.ac.uk
authors.forename: Alícia P
authors.initials: AP
authors.lastname: Higueruelo
authors.forename: Adrian
authors.initials: A
authors.lastname: Schreyer
authors.forename: G Richard J
authors.initials: GR
authors.lastname: Bickerton
authors.forename: Will R
authors.initials: WR
authors.lastname: Pitt
authors.forename: Colin R
authors.initials: CR
authors.lastname: Groom
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D030562:Databases, Protein; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins