The inhibition of kinases has been pursued by the pharmaceutical industry for over 20 years. While the locations of the sites that bind type II and III inhibitors at or near the ATP binding sites are well defined, the literature describes ten different regions that were reported as regulatory hot spots in some kinases and thus can act as potential target sites for type IV inhibitors. We describe Kinase Atlas, a systematic collection of binding hot spots located at the above ten sites in 4910 structures of 376 distinct kinases available in the Protein Data Bank. The hot spots are identified  by FTMap, a computational analogue of experimental fragment screening. Users of Kinase Atlas may view summarized results for all structures of a particular kinase, such as which allosteric sites are present on the kinase and how druggable they are, or they may view or download hot spot information for a particular kinase structure of interest. The resource can thus be used either to discover where to target a kinase of interest, or whether a kinase is worth targeting at all, as some kinases do not have any structures with strong enough binding hot spots to be considered druggable. The use of the server is demonstrated by the identification of molecular probes that bind at the PIF pocket of CDK2, and allosterically regulate CDK2. Kinase Atlas, is available at https://kinase-atlas.bu.edu.<br/>

Kinase atlas: Predicted regulatory hot spots in kinases

2019 Fall National Meeting

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