Pharmacophore-based virtual screening, molecular docking and molecular dynamics studies for the discovery of novel...

The in silico evaluation of 27 p-aminosalicylic acid derivatives, also referred to as neuraminidase inhibitors was the focus of the current study. To search and predict new potential neuraminidase inhibitors, this study was based on the ligand-based pharmacophore modeling, 3D QSAR, molecular docking, ADMET and MD simulation studies. The data was generated from recently reported inhibitors and divided into two groups, one of these group has 17 compounds for training and the second group has 10 compounds for testing purpose. The generated pharmacophore has known as ADDPR_4 was found statistically significant 3D-QSAR model owing the high trust scores (R² = 0.974, Q² = 0.905, RMSE = 0.23). Morever external validation was also employed to evaluate the prediction capacity of the built pharmacophore model (R²_pred = 0.905). In addition, in silico ADMET, analyses were employed to evaluate the obtained hits for drug likeness properties. The stability of formed complexes was further evaluated using molecular dynamics. Top two hits showed stable complexes with Neuraminidase based on calculated total binding energy by MM-PBSA.Communicated by Ramaswamy H. Sarma.