Strategies for modeling the interactions of transmembrane helices of G protein-coupled receptors by geometric complementarity using the GRAMM computer algorithm

The progress in comparative modeling of globular proteins is based on the large number of available structural templates. At the same time, the importance of GPCR modeling studies that are not based on structural templates comes from the fact that out of >1000 known GPCRs, only one such potential template exists (rhodopsin). The similarity between protein docking and helix–helix packing is used and the protein docking procedure GRAMM is applied to the matching of helices in the TM bundle. GRAMM is based on the search for the steric complementarity at variable resolution. It is shown in the chapter that the steric interactions between TM helices are correlated with the helix–helix interaction energy to the degree that the steric interactions alone, in general, can be used to predict helix packing. The ability of GRAMM to predict the low-resolution match between the helices based on the smoothing of the energy landscape is demonstrated in this chapter. The existence of large-scale structural recognition factors in TM helices that facilitate the low-resolution match have been determined.