Fast prediction of hydration free energies from molecular interaction fields

• Published in: Journal of molecular graphics & modelling Vol. 20; no. 2; pp. 123 - 131
• Main Authors: Jäger, Robert, Kast, Stefan M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2001
• Subjects: Computer Simulation; Drug Design; GRID; Hydration free energy; Models, Chemical; Models, Molecular; Molecular surface; QSAR; Quantitative Structure-Activity Relationship; Solvation; Thermodynamics; Water; Molecular surface; Solvation; Hydration free energy; QSAR; GRID
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/S1093-3263(01)00108-5

A novel empirical model is presented that allows the fast computation of hydration free energies with high accuracy. The linear model is based upon the separation of the free energy of hydration into a cavity and an interaction term. The cavity contribution is modeled as a linear combination of molecular volume and surface terms. The interaction part is derived from the statistical three-dimensional (3D) free energy density and is modeled approximately as a molecular interaction field using the program GRID. A compression scheme is employed to represent this 3D information on the molecular surface by means of a linear combination of surface functions. A set of 81 small organic molecules with known experimental hydration free energies is used to determine the coefficients of the linear model by least squares regression. The fit is statistically significant yielding a correlation coefficient of 0.99, a root mean square error of 0.27 kcal/mol for the 81 molecules belonging to the training set, and 0.63 kcal/mol for an independent test set of 10 molecules.