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

The binding data for 27 analogues of thyroxine interacting with human prealbumin have been fitted to a simple distance geometry model of the binding site. The novel aspect of the calculation is that a general definition of chirality has been 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 analogues 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 to 1.6 A.