Protonation States and Conformational Dynamics in Ligand-Target Recognition and Binding

The correct chemical approach to molecular recognition and ligand binding (small molecules, drugs, and bio-molecules) to target biomolecules requires, in principle, the evaluation of the prototropic and conformational equilibria between the different protonation states (acidic, basic, and tautomeric) and conformers. These equilibria depend on the environment and on the target structural features (prototropic forms, conformational flexibility, folding/unfolding, etc.). Thus, prototropic and conformational ensembles of both ligands and targets are strictly interdependent and control molecular recognition and binding events in many bioprocesses. In this CPD issue some of the more representative approaches and applications presented by leading scientists in the field are collected in an attempt to illustrate the roles of prototropic and conformational ensembles of the interacting partners in molecular recognition, binding, information transfer, and functional responses.