Disallowed subpocket connections/special cases. As described in "Data and Methods", a few design choices were made to only allow the subpocket connections as depicted in Figure .C, defined based on prior investigation of known kinase inhibitors. 95.2% of the analyzed molecules follow this scheme, whereas (i) another 4.5% of the molecules could be rescued by the defined rules and (ii) the remaining 0.3% were discarded in this analysis as discussed in the following.