Protein Binding Pocket Steric Hindrance: Definition and Importance

The steric hindrance of the spatial occupancy of protein binding pockets refers to the obstruction or clashing of molecules due to their physical size and shape. This is a key factor in protein-ligand interactions, particularly in drug discovery. When a ligand attempts to bind to a protein binding pocket, the spatial arrangement of atoms within the pocket can prevent or hinder binding if the ligand is too large or if its shape does not fit perfectly. This steric hindrance significantly impacts the binding affinity, which is the strength of the interaction between the protein and the ligand. Understanding and manipulating steric hindrance is crucial for designing effective drugs that can bind to specific targets and exert their desired therapeutic effects.