Atomic Interactions and Profile of Small Molecules Disrupting Protein–Protein Interfaces: the TIMBAL Database
抄録
<jats:p>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 <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://www-cryst.bioc.cam.ac.uk/timbal">http://www‐cryst.bioc.cam.ac.uk/timbal</jats:ext-link></jats:p>
収録刊行物
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- Chemical Biology & Drug Design
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Chemical Biology & Drug Design 74 (5), 457-467, 2009-10-06
Wiley