Figure 4

Hit rates obtained for the 296 AIMS projects. (A) A comparison of hit rates using X-ray crystallography, NMR, Cryo-EM, and homology for modeling the structure of the proteins. Each point represents a project with the x-axis denoting the hit rate of the project (the percentage of molecules tested in the project that were active). The number of projects of each type is given in parentheses. We observed no substantial difference in success rate between the physical and the computationally inferred models. We achieved average hit rates of 5.6%, 5.5%, and 5.1% for crystal structures, cryo-EM, and homology modeling, respectively. The number of projects using NMR structures is too small to make statistically-robust claims. (B) A comparison of hit rates observed for traditionally challenging target classes such as protein–protein interactions (PPI) and allosteric binding. Of the 296 projects, 72 targeted PPIs and 58 allosteric binding sites. The average hit rates were 6.4% and 5.8% for PPIs and allosteric binding, respectively. (C) Comparison of hit rates observed for different target classes and (D) enzyme classes. No protein or enzyme class falls outside the domain of applicability of the algorithm.