Understanding Protein Targets

Understanding Protein Targets

In CADD, the target is a biomolecule, typically a protein, that a drug molecule is designed to alter the way it functions. Finding the right target is crucial for drug discovery to be effective. Not every protein involved in a disease is a good candidate for drug development. Selecting the right target is the most critical first step. 

Disease Relevance: The protein must have a proven role in the disease pathway. Evidence may originate from:

1. Genetics: Human genetic studies that connect changes in the protein to the disease.

2. Gene Expression: The protein is either too much or too little in diseased tissue.

3. Animal Models: Deleting or blocking the protein in an animal model alleviates disease symptoms.

4. Cellular Studies: Experiments conducted in cells demonstrate that the protein is essential for the disease process. 

Druggability: It is the chance that a small molecule that acts like a drug can change how a protein works. A druggable protein usually has:

1. A clearly defined binding pocket, like an enzyme's active site.

2. A pocket that is deep enough for a drug to fit snugly.

3. A chemical environment that lets strong, specific interactions happen, like hydrogen bonds and hydrophobic interactions.

4. Proteins that lack obvious pockets, such as some protein-protein interaction targets, are considered less druggable and more challenging to work with. 

Safety and Selectivity (Uniqueness): The best target should be:

1. Selective: The drug should only bind to the target protein and not to other proteins in the body that are similar to it. Off-target effects can cause side effects.

2. Safe: Modifying the target's activity shouldn't harm critical biological processes. 

Tractability (Experimental Feasibility): Is it possible to work with this protein?

Is it possible to make? The protein needs to be able to be produced and purified in large enough quantities for experiments.

Is there any structural data? Having a high-resolution 3D structure (in the PDB) significantly accelerates the drug design process.