Question

What is docking and how is it useful?

Answer 1

• Docking in the field of molecular biology is the study of how two or more molecular structures fit together. It is an invaluable tool in the field of molecular biology, computational structural biology or pharmacogenomics and is an important component of drug discovery toolbox.
• Docking is a molecular modelling technique that predicts the preferred orientation of how a protein interacts with small molecules (ligands), nucleic acids or other target proteins. Such simple bimolecular (protein-ligand) or supramolecular (protein-nucleic acid/ protein- protein) interactions are usually adjusted for to achieve the appropiate conformation, proper relative orientation, total energetic cost of the system and the overall "best fit". This is because proteins are flexible with variable degrees of freedom and their conformational space is also huge.
• Algorithmic based or computer simulated docking techniques are employed for intermolecular interactions which is based on shape complementarity and binding affinity. Shape complementarity between the solvent accessible areas of a receptor protein and the ligand's molecular surface determines the relative goodness-of-fit. Multiple combinations of protein-ligand duo based on shape complementarity can be generated and a scoring function needs to be assigned for the binding free energies of the interaction which determines the system's total energy for each conformational adjustment. This therefore determines the affinity of the ligand for its protein.

• Docking has several implications in the field of computer-aided drug designing and in the understanding of structural and molecular biology. As interactions between biologically relevant macromolecules or small molecules can play a central role in signal transduction, molecular docking has emerged to be a poweful technique to investigate such interactions.

1. In protein ligand interactions, docking helps to identify the target sites on the ligands surface which interacts with the target protein.
2. The mode of action of various enzymes can be understood using molecular docking.
3. In targeted drug-delivery system, one can explore the the size, shape, charge distribution, polarity, hydrogen bonding, and hydrophobic interactions of both ligand and the target macromolecule.
4. In computer aided drug designing, molecular docking can suggest all possible conformations in the huge energy landscape of a protein, thus saving time and cost to discover drugs by traditional experimental methods.
5. Due to the availability of several crystallized molecules and ligands, molecular docking can be used to study protein interactions, verify the crystallized compounds for interactions. The scoring function helps to select the best fit from an array of suitable protein-ligand orientations and conformations. Similarly active sites on the drugs/ compounds, active binding sites on the target protein for suitable test ligands and best possible binding orientation can be figured out using this tool.