Computer Aided-Drug Design (A Concept)

Just imagine how possible you could guess the binding affinities of several candidate drugs or already existing ones to their targets!
In drug design, their is always a goal and that is to be able to predict or guess if a molecule will bind to a target and the strength to which such a molecule can bind.
In simple terms, here is what CADD means: CADD utilizes Computational Chemistry to discover, enhance or modify, or study drugs and biologically active molecules.
Now, I want you to know a simple fact which I have somewhat said earlier and that fact is that CADD makes use of basic or simple knowledge of protein-receptor Chemistry in addition to bioinformatics to design drugs with the use of web-based tools, softwares and databases. The key factors involved in drug design include a receptor molecule and a protein molecule.
Let me make it a bit simpler. Do you recall the lock-and-key hypothesis for enzyme function? The hypothesis states that, "a receptor is complementary to a particular protein and when these two bind, conformational changes occur within the protein". 
Due to these conformational changes within the protein molecule, the protein either gets deactivated or activated, depending on the state that it was in earlier.

Now, when the enzyme dissociates from the protein molecule at a later point of time, the protein retains its older configuration and confirmation. So by applying this knowledge to CADD, one can state that the same happens when a receptor binds with a protein. A protein has some specific receptors and only those receptors that are specific to it can bind to that protein. Alright?
Protein-receptor specificity is indeed very interesting. Each protein has some specific receptors with which it binds. In CADD, the term ligand will be used for receptors. When a protein-ligand interaction occurs, conformational changes take place within the protein molecule. For a binding to occur between protein and ligand, specific amount of energy is required that is termed as BINDING ENERGY. During the binding, the particular amount of energy is released that is known as ACTIVATION ENERGY. For molecules that are less likely to bind together or have weak chemical interactions mixtures between them, more binding energy is required. Molecules having strong chemical interactions need quite a lower amount of energy.

In order for a drug to be designed, first of all, the protein molecule that has to be targeted is determined. The source of the protein molecules varies depending on the nature of the research being carried out. Usually a disease is targeted for which the drug is to be designed.
Several Databases are available that provides access to millions of protein and ligand molecules e.g RCSB and Zinc Database. Molecules are screened against a large library of compounds to get the molecules that bind with high affinity to the protein/receptor. Usually high binding affinity molecules are preferred.

Docking basically means binding of a protein and receptor molecules. The protein molecule is screened against a million compound library of ligand molecules. The data obtained is further fed into docking softwares like, MOE, DOCK or AUTODock, to perform the docking. The results are analysed on the basis of binding affinity and other parameters. The protein-ligand molecules with the highest binding affinities are selected and then analysed for further processing e.g Molecular Dynamics. The complex should have the highest binding affinity possible in order to make the perfect drug.

A good drug should have high specificity to its target. If a drug is not highly specific to its target, the results could be disastrous and there maybe side effects too.

This is my basic understanding of CADD and I hope you understand its importance in the scientific world!

#Raphael

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