Fig. 8.

Optimization of compound 8 for selective binding to 5-HT_1A over α₁-adrenergic receptor. 1a and 1b, Interactions of compound 8 with 5-HT and α₁, respectively. The dotted box represents the structural differences between the two target molecules. The authors leveraged this difference between the protein molecules to design a virtual analog of compound 8, identified as 20h. 2b and 2b, docking models of 20h into 5-HT and α₁. These docking modes indicate that the piperazine atom and aspartic acid interaction is maintained for 20h-5-HT complex and not for 20h-α₁ complex. An optimization strategy based on this observation was used to design the novel agonist PRX-00023 for treatment of anxiety and depression. Adapted from Becker et al. (2006).