Membrane-bound proteins molecular modeling

G-Protein-coupled receptors do not lend themselves to analysis by either NMR or x-ray crystallography due to their structural dependence on an intact cell membrane. In our laboratories we pursued this valuable structural information by utilizing a combination of structural homology modeling, molecular dynamics, systematic conformational searching methods, and mutagenesis experiments. The combination of these techniques led to a proposed model of bradykinin bound to the agonist site on its receptor [41]. 

Figure 18-8 Stereoscopic ribbon diagrams of the chicken bc1 complex (A) The native dimer. The molecular twofold axis runs vertically between the two monomers. Quinones, phospholipids, and detergent molecules are not shown for clarity. The presumed membrane bilayer is represented by a gray band. (B) Isolated close-up view of the two conformations of the Rieske protein (top and long helix at right) in contact with cytochrome b (below), with associated heme groups and bound inhibitors, stigmatellin, and antimycin. The isolated heme of cytochrome c, (left, above) is also shown. (C) Structure of the intermembrane (external surface) domains of the chicken bcx complex. This is viewed from within the membrane, with the transmembrane helices truncated at roughly the membrane surface. Ball-and-stick models represent the heme group of cytochrome cy the Rieske iron-sulfur cluster, and the disulfide cysteines of subunit 8. SU, subunit cyt, cytochrome. From Zhang et al.105...

---