Quantitative structure-activity relationships by distance geometry: thyroxine binding site

Abstract

The binding data for 27 analogs of thyroxine interacting with human prealbumin were fitted to a simple distance geometry model of the binding site. The novel aspect of the calculation is that a general definition of chirality was implemented, so that the model site exhibits the observed stereospecificity. The calculated free energies of binding of the ligands fit the experimental data with a root mean square deviation of 0.5 kcal/mol. Three additional analogs not included in the original data set fit equally well. The geometry of the proposed binding site matches the X-ray crystal structure of the tetraiodothyronine-prealbumin complex with a root mean square deviation of 1.0-1.6 .ANG.