BIOLOGY MOLECULAR MODELLING

Introduction:
Molecular docking analysis has been one of the most basic and important strategy for drug discovery. It allows prediction of molecular interactions that hold together a protein and a ligand in the bound state.(1)
Molecular docking is a technique that predicts the preferred orientation, affinity, and interaction of a ligand in the binding site of a protein. Information of the preferred orientation in turn may be used to predict the strength of binding affinity between a drug target and ligand molecule using scoring functions. Several docking tools, such as AutoDock, AutoDock Vina, Gilde, DOCK, GOLD, FlexX, and Surflex, and many docking servers, such as ZDOCK, HDOCK, ClusPro, and SwissDock, are available for molecular docking purposes. Several parameters, such as ligand center and the number of torsions, binding residues, grid parameters, flexible residues, algorithm, iteration, pose, and result oriented settings, are defined before proceeding for docking. Molecular docking is used for virtual screening, binding affinity, and binding free energy calculations and also for tracing out and visualizing various types of bonded and nonbonded interaction between the ligand and amino acid residues of a protein.(2)

Result:
We did a docking study with heme ligand of myoglobin protein.
mode |  affinity | dist from best mode
    | (kcal/mol) | rmsd l.b.| rmsd u.b.
-----+------------+----------+----------
  1        -0.0     0.000     0.000
  2        -0.0     4.373     8.795
  3        -0.0     4.231     9.414
  4        -0.0     4.590     6.945
  5        -0.0     6.359     8.243
  6        -0.0     4.165     7.454
  7        -0.0     3.827     7.937
  8        -0.0     4.797     7.904
  9        -0.0     3.407     6.861
Writing output ... done.
We obtained the above calculations with the help of computer. We calculated the preferred orientations of the ligand using the molecular docking technique. In the image above we see the different orientations of the ligand. For this, we used AutoDock, AutoDock Vina and Pymol programs.We observe protein and different orientations of ligand in the image.
Discussion:
We calculated 9 different orientations of the ligand and they all have different energies because the ligand interacts with the protein from different places and different angles, which changes the value of the energy released. Because different bonds and bond lengths are formed, in this case, the energy formed differs. By observing these differences, we can predict the binding affinity of a drug. Thus, with this protein-ligand docking process, drug design can be analyzed in a computer environment. Thus, time and cost savings can be achieved in drug design.
Reference:
1) https://www.sciencedirect.com/science/article/pii/B9780128205464000064
2) https://www.sciencedirect.com/science/article/pii/B9780323897754000109