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.
D001665:Binding Sites; D006801:Humans; D008433:Mathematics; D011228:Prealbumin / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000378:metabolism; D014961:X-Ray Diffraction
D011228:Prealbumin; D013974:Thyroxine