Docking

There are several reasons for our interest in docking problems:

• Rational drug design - When we develop a drug that is supposed to be docked on a specific known receptor, we have to adjust it to the receptor. The efficiency of drugs is often a function of the contact area between the ligand (drug molecule) and the receptor.
• Biomolecular structure recognition - The action of docking happens naturally when enzymes dock on proteins and react with them. Understanding this process is a part of understanding the reaction processes occuring in organisms.

The main idea of docking is the "key in lock". The ligand is a key - small and sometimes flexible. The receptor is the lock, big and usually with a low level of flexibility. The better these two molecules fit - the better the influence of the drug and the interaction between them, will be. Researches have shown that there are molecules that are not completely rigid, but have partial flexibility. Usually the flexibility is in some spots, called hinges, between two parts of the molecule. In the hinges there is usually a determined range of angles where the rigid parts can rotate (see figure 13.19).

  

Figure 13.19: A molecule (two rigid parts and one hinge) and a receptor

The class of docking problems has two major subclasses.

• The rigid docking problem (two rigid molecules - the simpler problem)
• The flexible docking problem - one (or both) of the molecules has some degrees of freedom. This problem is harder to solve.

When evaluating docking methods, one should examine the following issues:

• Does the method deal with rigid docking or flexible docking?
  If the method allows flexibility:
  • Is flexibility allowed for ligand only, receptor only or both?
  • What is the number of flexible bonds allowed and the cost of adding additional flexibility.
• Does the method require prior knowledge of the active site?
• Speed - ability to explore large libraries.

On figure 13.20 you can see a sketch of the different stages a docking method has.

  

Figure 13.20: Rigid and Flexible Docking.