Types of Binding Pockets

Binding pockets are not created equal. They can be classified based on their location and function.

Orthosteric pocket: The orthosteric pocket is the main binding pocket, which is the most obvious place for a protein to bind. It's where the protein's natural ligand binds. This is the active site in enzymes, where the main chemical reaction takes place. In structure-based drug design, most drugs (small molecules) are made to target orthosteric sites.

Allosteric pocket: We will call the allosteric pocket a secondary binding site that is not directly next to the orthosteric site. When a ligand binds here, it changes the shape of the protein, like a remote control. This change in shape affects the main (orthosteric) site, which can either make the protein work better or stop it from working. Allosteric drugs are an area of research that is growing because they can have more specific effects and fewer side effects.

Cryptic Pocket: This is a pocket that is hidden and can't be seen when the protein is inactive and not bound (apo). When a ligand binds, the protein structure changes, and the pocket opens up. Finding these is hard, but it opens up new options for drug targets.