Computer graphics in drug design: molecular modeling of thyroid hormone-prealbumin interactions.
Computer graphics modeling of the thyroxine-prealbumin complex provides a detailed picture of the interactions between thyroxine and prealbumin. A wide variety of thyroid hormone analogue-prealbumin complexes were modeled by calculating the molecular surfaces of the analogues and the prealbumin hormone-binding site. Analogues with high binding affinity were observed to fill more of the hormone-binding site than low-affinity analogues. These surface models described many aspects of the hormone-protein interaction which were not obvious using simple wire models and led us to develop a model which accounts for thyroid hormone-prealbumin structure-activity relationships and ultimately to predict and measure the relative binding affinities of four previously untested thyroid hormone analogues to prealbumin.
D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003201:Computers; D006801:Humans; D008958:Models, Molecular; D011228:Prealbumin / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013963:Thyroid Hormones / Q000097:blood*; D014961:X-Ray Diffraction
D011228:Prealbumin; D012709:Serum Albumin; D013963:Thyroid Hormones