Molecular dynamics exploration of protein–ligand interactions between c-kit and three benzothiazole-2-thiol derivatives

The c-kit tyrosine kinase receptor is a strategic therapeutic target involved in regulating signaling pathways that control tumor proliferation and survival. This study used a computational approach to explore protein-ligand interactions between c-kit and three benzothiazole-2-thiol derivatives (LIG24, LIG26, and LIG32) in order to identify drug candidates.

SwissADME software was used to estimate the pharmacokinetic properties (ADME) for this study. The electronic properties were evaluated using DFT calculations at the B3LYP/6-311++G(d,p) theory level with Gaussian 09 software. For the stability of c-kit-ligand complexes and ligand interactions in the c-kit catalytic pocket, a molecular dynamics simulation was performed using Desmond software over a period of 200 ns.

For each ligand, the results reveal pharmacokinetic profiles compatible with therapeutic application. All three complexes exhibit stability with stationary RMSD plateaus. The C-KIT–LIG26 complex stands out with the lowest potential energy. This complex exhibits a network of persistent interactions involving key residues in the active site (LYS623, ILE789, ASP810, and VAL654).

Finally, the results obtained indicate that the LIG26 ligand is a good drug candidate for developing a c-kit-targeting inhibitor for the treatment of HCC.