Docking and docking techniques & Applications

Docking and docking techniques & Applications, Everything you need to know to understand molecular docking and various techniques.

What is Docking?

Molecular docking is a study of “how two or more molecular structures”, match along to be a perfect fit with each other. For instance, a drug and a catalyst or macromolecule receptor.

It can also be explained as:

  • Docking is a structure-based study that attempts to find the best match between two molecules.
  • Docking is a method that predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex.
  • Knowledge of preferred orientation, in turn, may be used to predict the strength of association or binding affinity between two molecules using, for example, Scoring functions.
How a ligand binds to an active site based on the orientation

Why docking is important?

Molecular docking is an alluring platform to comprehend drug biomolecular associations for the sane medication structure and disclosure, just as in the unthinking investigation by setting a particle (ligand) into the favored restricting site of the objective explicit locale of the DNA/protein (receptor) primarily in a non-covalent design to frame a steady perplexing of potential viability and greater explicitness.

  • To understand cellular biology.
  • Key to rational drug design.

Steps involved in Molecular docking?

  1. Understanding the Structure of Target and Ligand.
  2. Locate the Binding site.
  3. Determination of the binding mode.
How docking takes place

Analyzing target structure

Firstly, the target 3D structure is required which can be obtained from the PDB database.

Multiple things need to be checked before further procedures. Example:

X-ray Diffraction

  • No limitations in size.
  • It should be accurate.
  • Unique crystal structure.
  • Bi crystallization problems.
  • Hydrogens are removed.


  • To check the lowest accuracy.
  • Solution structure.
  • Size limits around 150 residues for a protein.

Homology Modelling

  • Free and quick analysis.
  • Low precision of sidechains.
  • Maximum sequence similarity and identity.

Analyzing ligand structure

Ligands are generally molecular organic compounds. GUI (Graphical user interface) software is used running molecular mechanic theory such as Maestro, Sybyl, Accelrys, Meo, ICM, etc.

Ligand structure

Interacting sites

Rules to be followed:

How to find a perfect molecular docking technique:

  • It should have a reasonable computational time.
  • The global minimum of the target/ligand interaction energy should be reached.
  • Free energies help reproduce experimental calculation.
  • Experimental interaction patterns observed in X-ray complexes should be identical.

Molecular docking is generally shared in two steps.

Molecular docking is shared in two steps.
How to build a successful docking program

Search Algorithm

  • Determining all possible optimal conformation for a given complex (Protein-Ligand/ Protein-Protein)
  • Calculate the total energy of the resulting complex with its individual interactions.

Conformational search strategies include:

  • Systematic/ stochastic torsional searches about the rotatable bonds.
  • Molecular dynamics simulations.
  • Genetic algorithms to evolve new low energy conformations.

Algorithms and Methods:

  • Grid Method
  • Sphere Method
  • Incremental Method

Grid Method – Type 1

A box is drawn on the protein macromolecule and the interaction is explored only on the subjected box. This limits the computational time required to evaluate the protein.

Grid Box

Make Sure:

  • If the box would be too small then the docking will be incorrect.
  • If the box is too big, exploration would become more extensive and would result in “False positive” results.
  • Take care of the amino-acids you want to embedded in the box(Especially the charged residues).

Grid Method

To ensure the global optimum, you have to explore the box.

It is a classical molecular modeling problem without an absolute solution“.

In docking several exploration methods (In Global Search) are used:

  • Molecular Dynamics
  • Simulated annealing
  • Generic Algorithm
  • Conjugated gradient

However, the best method is considered to be a genetic algorithm (Lamarckian) followed by some steps of the conjugated gradient.

Sphere Method – Type 2

This is a technique that mostly works on the shape of the molecules rather than the interactions complementarity.


  • Misses Sphere dimensions.
  • It doesn’t match sphere centers.
  • It does not meet ligand flexibility.

Incremental Method – Type 3

  • Splits ligands into base fragments and side chains.
  • Places the bases.
  • Adds side chains to grow(Scoring grows as you grow)

Eg: Umbrella Interaction

  • H-bond
  • Electrostatic
  • Hydrophobic contact

This method tends to overestimate the importance of H-bonds with other interactions.

Scoring Functions

Experimental scoring capacities are broadly utilized for posture and partiality forecast. In spite of the fact that present expectation is performed with agreeable precision, the right forecast of restricting proclivity is as yet a difficult errand and significant for the accomplishment of structure-based VS tests.

There are a few endeavors in unmistakable fronts to grow much increasingly advanced and precise models for separating and positioning huge libraries of mixes.


  • Quick computation
  • Able to compare results with the experimental data.
  • Able to distinguish between true inhibitors to false-positive ligands.
  • Able to rank ligands based on score.

Scoring Methods

  • Force field
  • Empirical potential
  • Knowledge-based

Force field

Empirical Potential

A function is designed to evaluate the free energy of binding instead of interaction energy.

Example: FlexX, Autodock, Gold, etc.


Conclusion of Automated Docking

Types of Docking

  • Lock and Key/ Rigid Docking
  • Induced fitting/ Flexible Docking

Rigid Vs Flexible Docking

  • Most of the early algorithms assumed that the docked molecules do not change conformations. This assumption allows treating the molecules as rigid bodies, making the algorithm simpler and faster.
  • This assumption is obviously problematic and was proven to be wrong in several cases.
  • Newer algorithms try to face flexibility problems in a variety of ways.
  • Other methods try to handle the flexibility problem indirectly or at least to “minimize the damage” of not incorporating flexibility.
  • Docking procedures that perform a rigid-body search are termed rigid docking.
  • Docking procedures that consider possible conformational changes are termed flexible docking.

Application of Molecular Docking

Molecular docking can exhibit the achievability of any biochemical response as it is done before an exploratory piece of any examination. There are a few regions, where atomic docking has upset the discoveries. Specifically, the connection between little particles (ligand) and protein target (might be a catalyst) may foresee the initiation or restraint of chemicals. Such sort of data may give a crude material to the judicious medication planning. A portion of the significant uses of atomic docking are depicted underneath: –

Lead optimization

Molecular docking can anticipate a streamlined direction of ligand on its objective. It can foresee diverse restricting methods of ligand ready for the target particle. This can be utilized to grow progressively powerful, particular and effective medication competitors.

Hit identifications

Docking in blend with scoring capacity can be utilized to assess huge databases for discovering powerful medication applicants in silico, which can focus on the particle of intrigue.

Drug-DNA interaction

Molecular docking assumes a conspicuous job in the underlying forecast of medication’s coupling properties to nucleic corrosive. This data builds up the connection between’s medication’s Molecular structure and its cytotoxicity.

Keeping this in see, therapeutic scientific experts are continually investing their amounts of energy to explain the fundamental anticancer component of medications at the atomic level by researching the communication mode between nucleic corrosive and medications in the nearness of copper.

Therapeutic physicists are doing in silico perceptions where their primary discovering is to anticipate whether the compound/sedate is connecting with the protein/DNA. On the off chance that the docking program is anticipating the said collaboration, at that point, the test methods are made accessible to discover the genuine restricting method of the complex.

This prompts the advancement of new anticancer medication. Moreover, this information would be instrumental in the identification of those basic changes in a medication that could bring about arrangement/structure explicit official to their objective.

Stay connected to learn more!

  1. Quite informative!!

Bioinformatics India