Desolvation energetics

DeChancie, J., Houk, K. N. The origins of femtomolar protein-ligand binding hydrogen-bond cooperativity and desolvation energetics in the biotin-(strept)avidin binding site. J. Am. Chem. Soc. 2007, 129, 5419-5429. 

The second group of studies tries to explain the solvent effects on enantioselectivity by means of the contribution of substrate solvation to the energetics of the reaction [38], For instance, a theoretical model based on the thermodynamics of substrate solvation was developed [39]. However, this model, based on the determination of the desolvated portion of the substrate transition state by molecular modeling and on the calculation of the activity coefficient by UNIFAC, gave contradictory results. In fact, it was successful in predicting solvent effects on the enantio- and prochiral selectivity of y-chymotrypsin with racemic 3-hydroxy-2-phenylpropionate and 2-substituted 1,3-propanediols [39], whereas it failed in the case of subtilisin and racemic sec-phenetyl alcohol and traws-sobrerol [40]. That substrate solvation by the solvent can contribute to enzyme enantioselectivity was also claimed in the case of subtilisin-catalyzed resolution of secondary alcohols [41]. 

Differential scanning calorimetry can also supply valuable information regarding solvate species, and it is particularly useful with respect to temperature and energetics of the desolvation process Two samples of the developmental compound L-706000-001T were shown to be chemically identical, and each contained two moles of water. The XRD powder patterns for the two samples were found to be quite different, demonstrating the existence of polymorphism... 

Not all structure-based design experiments are successful. Attempts to displace the arginine residue that caps the SI pocket of HFC by forming a salt link with carboxylate or hydroxyl moiety were unsuccessful [42]. However, these failed attempts offer some redeeming features in the refinement of parameters that can be used to evaluate the energetic potentials for displacing buried water molecules as well as the inherent desolvation energies for polar compounds. 

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