Modeling of G-Protein Coupled Receptors with Bacteriorhodopsin as a Template. A Novel Approach Based on Interaction Energy Differences

Abstract

The structure of bacteriorhodopsin was used as a template to generate a model for G-protein coupled receptors. However, these receptors and the template are not related by sequence homology. Therefore a pragmatic and reproducible approach was developed to achieve an energetically favourable accommodation of receptor sequences to the backbone structure of bacteriorhodopsin. Improved interaction energy differences are used in a two step procedure analogous to a hypothetical folding mechanism for integral membrane proteins. The resulting model is in good agreement with existing data from structure-function studies.