Novel approach to computer modeling of seven-helical transmembrane proteins: Current progress in the test case of bacteriorhodopsin

G-protein coupled receptors (GPCRs) are thought to be proteins with 7-membe red transmembrane helical bundles (7TM proteins). Recently, the X-ray struc tures have been solved for two such proteins, namely for bacteriorhodopsin (BR) and rhodopsin (Rh), the latter being a GPCR. Despite similarities, the structures are different enough to suggest that 3D models for different GP CRs cannot be obtained directly employing 3D structures of Bn or Rh as a un ique template. The approach to computer modeling of 7TM proteins developed in this work was capable of reproducing the experimental X-ray structure of BR with great accuracy. A combination of helical packing and low-energy co nformers for loops most close to the X-ray structure possesses the r.m.s.d. value of 3.13 Angstrom. Such a level of accuracy for the SD-structure pred iction for a 216-residue protein has not been achieved, so far, by any avai lable ab initio procedure of protein folding. The approach may produce also other energetically consistent combinations of helical bundles and loop co nformers, creating a variety of possible templates for 3D structures of 7TM proteins, including GPCRs. These templates may provide experimentalists wi th various plausible options for 3D structure of a given GPCR; in our view, only experiments will determine the final choice of the most reasonable 3D template.