Figure 5.

Binding mode analysis of the generated molecules for HPK1. (a) Glide Score distribution for active reference compounds and generated molecules. (b) Results of t-SNE clustering using IGM calculated NCIs as features. Red circles are used to indicate our generated molecules with novel cyclic skeletons³³ (CSK) with respect to reference compounds. A generated molecule is defined as having novel CSK if the highest Tanimoto similarity between its CSK and that of all the reference compounds is less than 0.5. (c) Binding mode of selected molecules generated by our model. (d) Binding mode of selected molecules generated by benchmark model. For panel c and d, NCI regions are indicated with dots colored using the rainbow scheme, in which blue indicates weak interactions and red indicates strong interactions. More details are provided in Supplementary material 4, 5, and 6.