title: GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome.
abstract: Experimental structure determination remains difficult for G protein-coupled receptors (GPCRs). We propose a new hybrid protocol to construct GPCR structure models that integrates experimental mutagenesis data with ab initio transmembrane (TM) helix assembly simulations. The method was tested on 24 known GPCRs where the ab initio TM-helix assembly procedure constructed the correct fold for 20 cases. When combined with weak homology and sparse mutagenesis restraints, the method generated correct folds for all the tested cases with an average Cα root-mean-square deviation 2.4 Å in the TM regions. The new hybrid protocol was applied to model all 1,026 GPCRs in the human genome, where 923 have a high confidence score and are expected to have correct folds; these contain many pharmaceutically important families with no previously solved structures, including Trace amine, Prostanoids, Releasing hormones, Melanocortins, Vasopressin, and Neuropeptide Y receptors. The results demonstrate new progress on genome-wide structure modeling of TM proteins.
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA; School of Mathematical Sciences and LPMC, Nankai University, Tianjin 300071, China.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Jang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA. Electronic address: zhng@umich.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D002462:Cell Membrane / Q000737:chemistry; D030562:Databases, Protein; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D008958:Models, Molecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D043562:Receptors, G-Protein-Coupled