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Updated: May 18, 2026

A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
Structure prediction of G protein-coupled receptors and their ensemble of functionally important conformations
Ravinder Abrol1, Adam R Griffith, Jenelle K Bray
1Materials and Process Simulation Center, MC, California Institute of Technology, Pasadena, CA, USA. abrol@wag.caltech.edu
Abstract:
G protein-coupled receptors (GPCRs) are integral membrane proteins whose "pleiotropic" nature enables transmembrane (TM) signal transduction, amplification, and diversification via G protein-coupled and β arrestin-coupled pathways. GPCRs appear to enable this by being structurally flexible and by existing in different conformational states with potentially different signaling and functional consequences. We describe a method for the prediction of the three-dimensional structures of these different conformations of GPCRs starting from their amino acid sequence. It combines a unique protocol of computational methods that first predict the TM regions of these receptors and TM helix shapes based on those regions, which is followed by a locally complete sampling of TM helix packings and their scoring that results in a few (~10-20) lowest energy conformations likely to play a role in binding to different ligands and signaling events. Prediction of the structures for multiple conformations of a GPCR is starting to enable the testing of multiple hypotheses related to GPCR activation and binding to ligands with different signaling profiles.
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