Molecular docking using Autodock vina

Molecular docking involves the computational exploration of a molecular search space defined by the method’s molecular representation. It entails ranking candidate solutions to identify optimal binding modes, necessitating both a search method and a scoring function. Primarily applied in ligand–protein docking, molecular docking has extended its utility to include protein–protein docking. Widely employed in drug discovery, it contributes to various aspects such as structure–activity studies, lead optimization, virtual screening for lead identification, facilitating mutagenesis predictions, aiding in substrate and inhibitor fitting to electron density in x-ray crystallography, chemical mechanism studies, and assisting in combinatorial library design. Molecular docking was performed using ADV to screen out the molecules having high-affinity and low binding energy. The ADV is an open-source, widely used molecular docking engine that uses a Monte Carlo (MC) [33] based search algorithm to explore the equal efficiency for its energy landscape. Validation of the molecular docking protocol is an essential step to verify the best-docked pose as comparable to the crystalized conformation [34]. For this purpose, the co-crystal ligand, TMP, was re-drawn and docked at the active site where the co-crystal ligand was bound. On successful docking, the best-docked pose was superimposed on a co-crystal ligand conformer, and RMSD was recorded [35]. The above step was repeated by varying the parameters. It is reported that the RMSD of ≤ 2 Å between best-docked pose and crystal conformation indicates the possibility of generation comparable conformation similar to the crystalization.

Prior to the docking, the crystal structure of TMK was obtained from the RCSB-Protein Databank (PDB) [36] having the PDB ID: 1G3U [37]. The selected protein structure consists of 214 amino acids with resolution and R-value of 1.95 Å and 0.250, respectively. The Autodock tool (ADT) was used to prepare the protein by repairing the missing atoms, adding hydrogens and Gasteiger charge, and saving in.pdbqt format, then assigning the AD4 atom types.

The small molecules were prepared using the OpenBabel tool. In particular, the molecules were converted into 3D format, added hydrogen and Gasteiger charges, and saved as.pdbqt and.mol2 formats for docking in ADV and PLANTS, respectively.