Structural Biochemistry/Molecular Moldeling/Molecular Docking

In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using for example scoring functions. Docking is frequently used to predict the binding orientation of small molecule drug candidates to their protein targets in order to in turn predict the affinity and activity of the small molecule. Hence docking plays an important role in the rational design of drugs. Given the biological and pharmaceutical significance of molecular docking, considerable efforts have been directed towards improving the methods used to predict docking. Molecular docking can be categorized into two main kinds as following: Rigid-flexible docking (also rigid docking) is the molecular docking which allows only ligand (donor or small molecule) to change its orientation (depending on its torsional degree of freedom) during docking calculation. Flexible-flexible docking (also flexible docking), in addition to rigid docking, macromolecule (protein enzyme) also change its orientation, especially around active site.

Molecular Docking Based Theory
Docking is based on equilibrium equation as following:  P(aq)  +  L(aq)  →    PL(aq)   Kb     =    $$\tfrac{[PL]}{[P][L]}$$ 	 ; binding constant   Kd     =    $$\tfrac{[P][L]}{[PL]}$$     	 ; dissociating constant 

 ΔGbinding = -RT lnKbundefined = RT lnKd  , where ΔGbinding is binding Gibb’s free energy  Binding energy indicates how good macromolecule and ligand can bind each other. Thus, even more negative binding energy, even more strength in binding between two molecules takes place. To succeed this case, Kb should be great or Kd should be low.

Scoring Function
Scoring functions are the answer to the first question, “How to calculate the interactions?” They can tell “how good” a ligand of specific conformation can bind to a receptor. Since the interaction between a ligand and a receptor is a “function of their conformations”, researchers have ideas of trying to “approximate the function” as closely as they can. The approximating functions constructed are called “scoring functions” which can be classified into two main group. The first group of functions contains scoring schemes based on physical interaction terms, such as Van der Waals interactions or hydrogen bonding. The binding interaction is calculated by the Lennard-Jones pair potential.