Quantum chemical, spectroscopic, and in silico molecular docking and molecular dynamics studies on thymotrinan, which has immunomodulatory and neuroprotective properties

Abstract

Thymotrinan is an immunomodulating tripeptide containing the Arg-Lys-Asp sequence.In this study, the structural, vibrational, and electronic properties, as well as the bioactivity of thymotrinan, have been thoroughly examined.The conformational preferences of thymotrinan were evaluated through conformational analysis, and the lowest-energy conformer was then optimized using DFT/WB97XD/6–31 + + G(d, p) theory level.The vibrational wavenumbers of the optimized structure were calculated, and the molecular electrostatic potential (MEP) and frontier molecular orbital (HOMO, LUMO) analyses were performed. To analyze how thymotrinan interacts with the α7 nicotinic acetylcholine receptor chimera and to evaluate its potential to inhibit α-Bungarotoxin, a snake venom protein, molecular docking studies were performed between thymotrinan and target proteins, including the α7nAchR chimera in complex with α-BTx(PDB ID 4HQP), the α7nAchR chimera without the α-BTx protein(α-BTx-removed 4HQP), and α-BTx(PDB code: 1IK8).Afterwards, the thymotrinan-1IK8 complex was subjected to 200 ns of all-atom molecular dynamics (MD) simulations to demonstrate its stability.Based on the MD trajectory, the binding free energy of the complex was estimated to be -18.545 kcal/mol using the MM-PBSA method.In addition, in silico pharmacological predictions suggest that thymotrinan may exhibit anticancer activity against multiple cancer cell lines and antibacterial activity against a range of bacterial species. However, experimental validation of these findings remains required.