On the possibility of the existence of orienting hydrodynamic steering effects in the kinetics of receptor–ligand association

In the vast majority of biologically relevant cases of receptor-ligand complex formation, the binding site of the receptor is a small part of its surface, and moreover, formation of a biologically active complex often requires a specific orientation of the ligand relative to the binding site. Before the formation of the initial form of the complex, only long-range, electrostatic and hydrodynamic interactions can act between the ligand approaching the binding site and the receptor. In this context, the question arises whether as a result of these interactions, there is a pre-orientation of the ligand towards the binding site, which to some extent would accelerate the formation of the complex. The role of electrostatic interactions in the orientation of the ligand relative to the binding site of the receptor is well documented. The analogous role of hydrodynamic interactions, although assessed as very significant by Brune and Kim (PNAS 91, 2930–2934, (1994)), is still debatable. In this article, I present the current state of knowledge on this subject and consider the possibilities of demonstrating the orienting effect of hydrodynamic interactions in the processes of receptor–ligand association, in an experimental way supported by computer simulations.