Comment on ‘Molecular driving forces of the pocket-ligand hydrophobic association’ by G. Graziano, Chem. Phys. Lett. 533 (2012) 95

We comment on a study by G. Graziano recently published in Chem. Phys. Lett. 533 (2012) 95, which presented an alternative interpretation of our previous study on hydrophobic cavity–ligand association [P. Setny, R. Baron, J.A. McCammon, J. Chem. Theory Comput. 6 (2010) 2866]. Here, we show why this interpretation is not appropriate in the context of cavity–ligand binding. We also demonstrate that a thorough understanding of an association process can be achieved only after considering all entropic and enthalpic contributions, including also those that cancel with each other.