Fig. 4.

a A hydrophobic hotspot in the c-Abl myristoyl site identified by a multi-fragment search and the snug fit of dihydropyrazole analog 7 to this hotspot. The surface of the myristoyl site is shown in pink, with that of the hydrophobic hotspot in green. The three residues comprising the hotspot (i.e. Ala356, Leu359 and Tyr454) are rendered in stick format. The surface of the docked pose of 7 is shown in a dotted representation and is in pink. b The docked pose of 9 in the myristoyl site with the bent C-terminal helix. The surfaces of Val525 and t-butyl moiety of 9 are shown in dotted representations and are in green and pink, respectively. The hydrogen bond between 9 and Arg351 is represented by a dash line. c The docked pose of 9 in the myristoyl site with the straight C-terminal helix. The hydrogen bond between 9 and Y454 is represented by a dash line; so is the electrostatic interaction between 9 and Arg351