CHIPMUNK: A Virtual Synthesizable Small-Molecule Library for Medicinal Chemistry, Exploitable for Protein-Protein Interaction Modulators.
A common issue during drug design and development is the discovery of novel scaffolds for protein targets. On the one hand the chemical space of purchasable compounds is rather limited; on the other hand artificially generated molecules suffer from a grave lack of accessibility in practice. Therefore, we generated a novel virtual library of small molecules which are synthesizable from purchasable educts, called CHIPMUNK (CHemically feasible In silico Public Molecular UNiverse Knowledge base). Altogether, CHIPMUNK covers over 95 million compounds and encompasses regions of the chemical space that are not covered by existing databases. The coverage of CHIPMUNK exceeds the chemical space spanned by the Lipinski rule of five to foster the exploration of novel and difficult target classes. The analysis of the generated property space reveals that CHIPMUNK is well suited for the design of protein-protein interaction inhibitors (PPIIs). Furthermore, a recently developed structural clustering algorithm (StruClus) for big data was used to partition the sub-libraries into meaningful subsets and assist scientists to process the large amount of data. These clustered subsets also contain the target space based on ChEMBL data which was included during clustering.
['Humbeck|Lina|L|0000-0003-3151-9158', 'Weigang|Sebastian|S|', 'Schäfer|Till|T|0000-0003-1709-1925', 'Mutzel|Petra|P|0000-0001-7621-971X', 'Koch|Oliver|O|0000-0001-9228-217X']
D000465:Algorithms D002626:Chemistry, Pharmaceutical D016000:Cluster Analysis D015195:Drug Design D011485:Protein Binding D011506:Proteins D054852:Small Molecule Libraries
virtual libraries protein-protein interaction inhibitors beyond rule of five heterocycles in silico reactions multiple component reactions