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. 2024 Apr 1;4(4):1632–1645. doi: 10.1021/jacsau.4c00123

Figure 1.

Figure 1

Structure and binding kinetic properties of the 132 N-HSP90α inhibitors. (A) Distribution of binding kinetic parameters for the N-HSP90α inhibitor data set. (B) Similarity matrix of the 132 N-HSP90α inhibitors generated by the Canvas Similarity and Clustering module of Maestro (Schrödinger, 2023). The figure shows the four major scaffold types of compounds, ① hydroxy-indazole, ② resorcinol, ③ quinazoline, and ④ 7-azazindole derivative; The R1 substituent is located near the hydrophilic ATP pocket, and the R2 substituent points to the hydrophobic pocket. (C) The alignment of complex structures of N-HSP90α featuring four different conformations in the data set (PDB IDs: 1OSF, blue; 5J20, cyan; 5NYH, magenta; 3TUH, orange) (the number of compounds is in parentheses). (D) Statistical distribution of dissociation rate constant of inhibitors with loop-in conformation and helical conformation. (E) Correlation analysis between the molecular weight of various inhibitors and the dissociation rate constant.