Hydration free energy a fragmental model and drug design.
The aim of this work was to provide a simple model to determine hydration free energies of molecular compounds at ambient temperature in order to help drug design. Since the free energy of interaction between molecules and water can be approximated by an additive function of their constituent groups, a model based on a fragmental analysis was developed with all the hydration free energies determined from experimental values. The model gives accurate hydration free energies on small molecules by simply adding the hydration energies of the fragments constituting the molecule. The correlation factor r(2) is 0.990 on the 125 molecules used to establish the model parameters. As experimental values are determined at ambient temperature (25 degrees C), the values obtained from the model will correspond to this temperature. For mean size molecules or big molecules as proteins, it was not possible to calibrate the model owing to the absence of experimental values. However, the model makes it possible to estimate the hydration free energy of such molecules. The fragmental representation of any molecule with coded colours, depending on the fragment nature (hydrophobic, hydrophilic or neutral), can be useful to understand molecule behaviour and help drug design.
Pèpe
Gérard
G
Groupe de Chimie Organique et Physique de Luminy, Faculté des Sciences de Luminy, Université de la Méditerranée, UMR-CNRS 6114, case 901, F-13288, Marseilles, Cédex 09, France. pepe@luminy.univ-mrs.f
Guiliani
Gaël
G
Loustalet
Sophie
S
Halfon
Philippe
P
D015195:Drug Design; D004798:Enzymes / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000737:chemistry; D008958:Models, Molecular; D019438:Ritonavir / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D004798:Enzymes; D017320:HIV Protease Inhibitors; D014867:Water; D019438:Ritonavir