NSGASEAL application: Electrostatics of selective serotonin reuptake inhibitors (SSRI's)

Despite the lack of 3D information of the target and the very flexible structure of the agonists our ligand based SEAL method will rapidly identify the underlying steric and electronic similarity of a the compounds and provide an intuitive insight into their binding modes. The figure below shows a number of well known selective serotonin reuptake inhibitors (and one putative one). The lowest energy conformer of the most rigid compound, Sertralinae, was used as template. Subsequently Alaproclate, Escitalopram, Etoperidone, Fluoxetine, Fluvoxamine, Paroxetine, and Zimelidine were flexibly aligned by means of simultaneous optimization of internal strain and electrostatic and steric overlap integrals.