Electrostatic potential and non-covalent interactions analysis for the design of selective 5-HT7 ligands

Despite the significant improvement of methodology in the field of the in silico drug discovery, the search for selective drugs is still far from trivial. This is especially relevant in the case of designing new medicaments for treatment of central nervous system disorders. In this work, we present a new approach based on the molecular docking and the following electronic properties analysis of ligands' binding poses (electrostatic potential distribution analysis and quantitative topological analysis of the electron density distribution). The proposed protocol significantly increases the success rate of the selective 5-HT7R ligands against 5-HT-R-1A selection from the prepared databases (the rise from 33.3% to 77.8% and from 22.7% to 62.5% for training and testing sets, respectively). The presented approach can be applied as a supportive method in the virtual screening of ligands databases. (C) 2019 Elsevier Inc. All rights reserved.