Theoretical Analyses on Interactions between GPCR and Ligand Compounds with Fragment Method

利用片段密度泛函理论（Fragment Density Functional Theory， FDFT）分析了β肾上腺素能受体氨基酸残基与配体化合物之间的相互作用能，确定了这些配合物的活性位点。在β1、β2、β3受体的相同位置上观察到配体与ASP之间的强吸引相互作用。此外，相同位置的SER与激动剂相互作用良好，但与拮抗剂几乎没有相互作用。发现SER与激动剂的相互作用能与EC50值相对应。因此，我们认为受体中的ASP和SER分别是主要的结合位点和活性位点。

The interaction energies between the amino acid residues inβadrenergic receptors and ligand compounds were analyzed with Fragment Density Functional Theory (FDFT), to assign active sites of these complexes. The strongly attractive interactions between the ligands and ASP at the same positions of the respectiveβ1,β2,β3receptors, were observed. Furthermore, SER at the same positions attractively interacted with the agonists, but hardly with the antagonists. The interaction energies between the SER and the agonists were found to be corresponding to the EC50 values. Therefore, it was concluded that the ASP and SER in the receptors were the major binding and active sites, respectively.