Application of HINT interaction scores and Hydropathic Intermolecular Field Analysis (HIFA) to the prediction of ligand binding affinity

COMP 102

Simon F. Semus, Computational, Analytical and Structural Sciences, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406 and Glen E. Kellogg, Department of Medicinal Chemistry, Virginia Commonwealth University, School of Pharmacy, Richmond, VA 23298.
HINT calculates empirical atom-based hydropathic parameters that are believed to encode all significant intermolecular and intramolecular non-covalent interactions implicated in drug binding or protein folding. Coulombic, hydrogen-bonding, dispersion, as well as hydrophobic effects may be extracted from the hydrophobic atom constant. Also significant is that since hydrophobicity is defined in terms of solubilities, the effects of solvent are also encoded within the constants. Hydropathic Intermolecular Field Analysis (HIFA) is a structure-based QSAR method, in a similar vein to CoMFA, that employs empirically derived hydropathic fields generated by HINT. Ligand-receptor HINT interaction fields are calculated for all molecules and imported in to a Sybyl spreadsheet, where the HIFA model is generated in a manner akin to CoMFA using PLS with cross-validation. It should be emphasized that whereas CoMFA measures the interaction between test ligands and a probe atom, HIFA captures the interaction between the ligand and the receptor.

Docking and Scoring
1:30 PM-4:50 PM, Tuesday, August 24, 2004 Pennsylvania Convention Center -- 109B, Oral

Division of Computers in Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004