Molecular insights into binding of bioactive compounds from essential oil of with human programmed cell death protein 1.

The human programmed cell death protein 1 (PD-1) is expressed on the surface of T cells and contributes significantly to tumor immunity. Herein, six major compounds (carvacrol, thymol, β-phellandrene, α-terpinene, myrcene D, and α-pinene) from were studied for their intermolecular interactions and stability against PD-1. All tested compounds displayed docking energy (-4.2 to -3.7 kcal/mol) with PD-1. The highest docking scores of -4.2 and -4.1 kcal/mol were recorded for carvacrol and thymol, respectively. Also, a 100 ns molecular dynamics simulation predicted the stability of carvacrol- and thymol-docked PD-1 complex. Maximum of < 30 Å and < 12 Å root-mean-square deviation were observed for carvacrol and thymol at the end of the 100 ns simulation with respect to protein (Cα atoms), indicating retention and displacement of carvacrol and thymol from the initial binding pocket, respectively. Moreover, the endpoint binding free energies support the higher binding affinity of carvacrol (-22.87 ± 5.52 kcal/mol) than thymol (-16.83 ± 1.30 kcal/mol). The equicrural states of the respective ligands were supported by the respective root mean square fluctuation, where no significant deviations in the atoms of the ligands were observed. These findings suggest that carvacrol and thymol inhibit the PD-1/PD-L1 axis.Communicated by Ramaswamy H. Sarma.