Comparative in silico molecular docking analysis of l-threonine-3-dehydrogenase, a protein target against African trypanosomiasis using selected phytochemicals

Abstract

Introduction: African trypanosomiasis is a neglected tropical disease caused by protozoa Trypanosoma brucei and transmitted via the bite of tsetse fly. The target protein of T. brucei is L-threonine-3-dehydrogenase, which has been selected for this study due to its metabolic importance for the parasite’s survival. Docking of target protein was carried out with phytochemicals that passed in silico drug-likeness filters and have in vitro anti-trypanosomal activity along with the standard drugs eflornithine and pentamidine available against the disease. Materials and Methods: A 3D structure of L-threonine-3-dehyrogenase was downloaded from Protein Data Bank (PDB) with Id: 5K4Y and Pictorial database of 3D structures in the Protein Data Bank (PDBsum) was used to retrieve the active sites of the protein. The reviewed ligands were screened using SwissADME, Lipinski’s rule of 5, and Molinspiration servers along with standard drugs and docked using AutoDock Vina and AutoDock 4.2.6. The 2D and 3D interacting residues were observed using Discovery Studio. Results: Ligand Camptothecin which inhibited T. brucei during in vitro cytotoxic assays gave better binding affinity scores than the standard drugs (eflornithine and pentamidine) selected for this study. Camptothecin showed interaction with those active site residues where ligand NAD (nicotinamide-adenine-dinucleotide) binds to the target protein, which is a significant restricting pocket for the hindrance of the parasite. Conclusions: Camptothecin derived from Camptotheca acuminata trees has the potential to be used as a better alternative than the standard drugs because of its less toxicity, better binding affinity, and specificity towards the inhibition of target protein.