Molecular Dynamics Simulation of Serotonin Transport Protein Complex with 6-Hydroxy-1-Methyl-1,2,3,4-Tetrahydro-β-Carboline Ligand from Chocolate (Theobroma cacao L.) Isolate

Abstract

6-hydroxy-1-methyl1,2,3,4-tetrahydro-β-carboline (6OHMTHβC) is a chocolate derivate that has antidepressant potency. It can increase dopamine and serotonin secretion, which leads to mood improvement. This method was carried out using computational molecular docking simulations (in silico). The research design was computational-based exploratory descriptive. The results of molecular docking showed the lowest energy score and the backbone RMSD value ≤2Å. The procedure performed was 6AWP receptor docking without ligand, with native ligand (6OHMTHβC), and with reference ligand (fluvoxamine). This study also performed molecular docking simulations of 6OHMTHβC towards 6AWP to find compounds in the receptor binding pocket. This study also performed dynamics simulations and identified the molecular determinants using PyPLIF-HIPPOS and YASARA Structure software 20.1.24.10 with the Windows 10 operating system. This study succeeded in determining the stability of the dynamics simulation of the serotonin transport protein complex with the reference ligand 6OHMTHβC for 50 ns, and this result corresponds to the RMSD value and binding energy. The determination of binding energy (BE) was calculated from the BE calculation available at YASARA and Ubuntu. The binding energy value of the original ligand was -11.6590 kJ/mol, and the reference ligand was -83880 kJ/mol. The highest RMSD value of the original ligand was 1.39292Å, while the RMSD value of the reference ligand was 1.71072Å. The essential amino acid carried out was 438Ser with hydrogen bond interactions, so 6OHMTHβC was considered a competent antidepressant candidate.