GPCR-I-TASSER: A hybrid approach to G protein-coupled receptor structure modeling and the application to the human genome
By Jian Zhang, Jianyi Yang, Richard Jang, Yang Zhang. 2015
152 citations recorded by the source corpus.
SUMMARY Experimental structure determination remains very 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 C-alpha RMSD 2.4 Å in the TM-regions. The new hybrid protocol was applied to model all 1026 GPCRs in the human genome, where 923 have a high confidence score that 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 transmembrane proteins.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Spectroscopy
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cellular and Molecular Neuroscience
In Molecular Biology
- Robin Pearce
- Jens Meiler
- Yang Zhang
- Brian Joseph Bender
- Brennica Marlow
- Jianyi Yang
- Michael Feig
- Ambrish Roy
In Spectroscopy
Citations in the corpus
- Improving homology modeling from low-sequence identity templates in Rosetta: A case study in GPCRs (2020, methodology): “For the C5aR1 structure, GPCR-I-Tasser just barely achieves a better RMSD for the full model (1.649 vs 1.661 Å).”
- Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases (2017, unknown): “Currently, the structures of about fifteen human GPCRs, including chemokine receptors CXCR4, CCR5 and CXCR1 are available [85].”
- Toward the solution of the protein structure prediction problem (2021, methodology): “To help partially overcome this, specialized methods have been designed to predict structures for these classes of proteins (110, 111).”