The ligand binding pockets of proteins have preponderance of hydrophobic amino acids and are typically within the apolar interior of the protein; nevertheless, they are able to bind low complexity, po
Changes of protein conformational entropy ΔS_conf and hydration layers are relevant for ligand-binding. The protein-ligand binding is governed by equilibrium thermodynamics ΔG=ΔH-TΔS, it occurs if ΔG
In lead optimization, open, solvent-exposed protein pockets are often disregarded as prospective binding sites. Because of bulk-solvent proximity, researchers are instead enticed to attach charged pol