Interface Prediction for GPCR Oligomerization Between Transmembrane Helices.

Oligomers of G protein-coupled receptors (GPCRs) are closely related to their biochemical and biological functions and have been conserved during the course of molecular evolution. The mechanisms of GPCR interactions and the reason why GPCRs interact between themselves have remained elusive. Accurate interface prediction is useful to generate guidelines for mutation and inhibition experiments and would accelerate investigations of the molecular mechanisms of GPCR oligomerization and signaling. We have developed a method to predict the interfaces for GPCR oligomerization. Our method detects clusters of conserved residues along the surfaces of transmembrane helices, using a multiple sequence alignment and a target GPCR or closely related structure. This chapter outlines our method and introduces some problems that occur with it, along with our future direction to extend the method for interface predictions of general membrane proteins.