Molecular Docking

Molecular docking is a method of studying the interaction between two molecules known as receptor molecules and the ligand molecule. The purpose of this method of docking is to predict the structure of the complex formed after the interaction of the ligand and receptor molecule through computation method. To understand further it is necessary to know what are a ligand and a receptor molecule, in common terms they are both proteins. The receptor molecule is often justified as a small protein molecule that is mobile with the body system such as hormones, enzymes and so. Whereas the ligand molecule is a bigger protein complex with different combinations of proteins bonded together having different protein receptors within them. 

This method of docking is a combination of different algorithms functioning together to compute the ligand-receptor interaction in all conformational sites possible of the protein.  Throughout this docking, the basic concept of geometrical and chemical matching are used to study the stereo fit or the chemical complementation between the active site of the receptor and ligand molecular complex. When considering the complementation of the fitting it is always based on the intermolecular bonds and the molecular properties with reference to the induced fit paradigm. This induced fit paradigm suggests the binding mechanism of both the interacting molecule based on the property of flexibility and rigidity. It suggests the binding mechanism of the molecules with the change in conformation for a tight fit between the interacted molecular complexes.

This method of molecular docking also provides predictions based on the binding energetic along with a ranking system for the interacting compounds with reference to its binding affinity or the electronic transfer between the complexes setting the basics of bonding of the ligand-receptor complexes.

(By : Scigenis, 2015)

Factors affecting molecular docking 

When considering molecular docking it is more of a dry lab work considering all the external and molecular factors affecting the complex interaction. Thus some of the common factors affecting the interactions are the following 

• Gibbs free energy 

• Binding constant 

• Formal charges 

• Electronegativity 

• Molecular mass

1. Gibbs free energy 

The Gibbs free energy is the measure of the work done in the interaction between two molecules forming complexes. It measures the maximum of work or energy in between the bonds of a molecular complex that can be used with an effective binding. This quantity determines how spontaneous the process of binding is with reference to the equilibrium point of the interaction taking place. The lower is the Gibbs free energy, the spontaneous is the interaction.

2. Binding constant 

The binding constant or also known as the inverse of the dissociation constant suggests the tightness or the strength of the bonds between the molecular complexes. The higher is the binding constant the smaller is the dissociation constant and thus leading a tighter fit between the molecular complexes.

3. Formal charges 

The quantity of formal charges is also considered as a variable affecting the interaction between the protein complexes as it measures the charge distribution at the atomic level with considering the binding interactions. To begin with, the basic reason for an interaction to happen between two molecules (that is bonding) is with the basic units like electrons involved. The main reason for the interaction below molecules to process is due to loss or gain and sharing of electrons. With reference to the experimental study, this particular property suggests the balance and stability of the docked complex with the base of the electron distribution. And hence linking to the concept of electronegativity. 

4. Electronegativity

This property or a quantity of measure accounts for the ability of the binding interaction with considering the formal charges and the share of electron distribution within the complex. A positive value of formal charge suggests the complex to be less electronegative and thus leading to an unstable complex as the charge distribution and the sharing of electrons within the bonds is weak. whereas for a negative formal charge, the electronegativity of the complex is high and thus suggesting a flexible docking complex with even charge or strong binding charge distribution.

  

5. Molecular mass

This is the sum of the atomic mass of all the atoms included within the complex formed. For a smaller molecular mass of a compound the binding interaction is much faster compared to a greater molecular mass. This is because it considers the flow and the charge density within the compound when considering the rate of the interaction between the molecules to form a complex.