Enhancing the Antipsychotic Effect of Risperidone by Increasing Its Binding Affinity to Serotonin Receptor via Picric Acid: A Molecular Dynamics Simulation

Abstract

The aim of this study was to assess the utility of inexpensive techniques in evaluating the interactions of risperidone (Ris) with different traditional -acceptors, with subsequent application of the findings into a Ris pharmaceutical formulation with improved therapeutic properties. Molecular docking calculations were performed using Ris and its different charge-transfer complexes (CT) with picric acid (PA), 2,3-dichloro-5,6-dicyanop-benzoquinon (DDQ), tetracyanoquinodimethane (TCNQ), tetracyano ethylene (TCNE), tetrabromo-pquinon (BL), and tetrachloro-p-quinon (CL), as donors, and three receptors (serotonin, dopamine, and adrenergic) as acceptors to study the comparative interactions among them. To refine the docking results and further investigate the molecular processes of receptor–ligand interactions, a molecular dynamics simulation was run with output obtained from AutoDock Vina. Among all investigated complexes, the [(Ris) (PA)]-serotonin (CTcS) complex showed the highest binding energy. Molecular dynamics simulation of the 100 ns run revealed that both the Ris-serotonin (RisS) and CTcS complexes had a stable conformation; however, the CTcS complex was more stable.

Design, synthesis, anti-proliferative evaluation, docking, and MD simulations studies of new thiazolidine-2,4-diones targeting VEGFR-2 and apoptosis pathway

“…Chemoinformatics (in silico techniques) was used as an efficient approach in drug discovery with the advantage of saving time, effort, and costs [11][12][13]. This includes molecular docking [14,15], ADMET assessment [15] and MD simulation techniques [14,16].…”

Protective effect of the newly synthesized and characterized charge transfer (CT) complex against arecoline induced toxicity in third-instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg9: experimental and theoretical mechanistic insights

“…A cooperative host–guest complexation may enhance the host conformation rigidity and thus increase its fluorescence. 77…”

Anticancer Activities of Re(I) Tricarbonyl and Its Imidazole-Based Ligands: Insight from a Theoretical Approach

“…While the negative binding energy observed in the other eight complexes results from the consumption of minimal energy from the ligand. The more negative the binding energy, the greater the stability of the complex, and the more positive the binding energy of the complex, the lesser the stability of the complex . Therefore, higher negative binding energy denotes better stability of the complex, thereby influencing the reactivity and potency of the drug.…”