Molecular dynamics simulations have shown that the concave pocket-convex ligand hydrophobic association is enthalpy-driven due to water reorganisation [11]. A different theoretical analysis is provided, grounded on the basic notion that the Gibbs energy gain upon association is mainly due to the decrease in the solvent-excluded volume, that translates in a gain of configurational-translational entropy of water molecules. It is also underscored that the reorganisation of water-water H-bonds is characterised by an almost complete enthalpy-entropy compensation and cannot affect the Gibbs energy change. (C) 2012 Elsevier B. V. All rights reserved.