|William L. Jorgensen, Department of Chemistry, Department of Chemistry, Yale University, New Haven, CT 06520-8107|
|Computational tools have been developed for the rapid prediction of properties of organic molecules that are relevant to their potential as drugs. A small number of physically significant descriptors, especially surface area components and hydrogen-bonding potentials, are computed from an input three-dimensional structure. Simple linear regression equations have been developed from experimental datasets using these descriptors for the accurate prediction of a variety of properties including aqueous solubility, octanol/water partition coefficient, free energy of hydration, Caco-2 and MDCK cell permeabilities, serum protein binding, and brain/blood partitioning. Other developments include a rule-based system for prediction of primary metabolites, while a more quantitative approach has been used in the computation of pKa values (acidities). The algoritms have formed the basis of the QikProp program.|
Prediction of Drug Solubility from Structure. W. L. Jorgensen and E. M. Duffy, Adv. Drug Delivery Reviews, 54, 355-366 (2002).
Herman Skolnik Award Symposium
2:00 PM-4:20 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 110A&B, Oral