This title appears in the Scientific Report :
2017
Please use the identifier:
http://dx.doi.org/10.1371/journal.pcbi.1005381 in citations.
Please use the identifier: http://hdl.handle.net/2128/13886 in citations.
Unifying view of mechanical and functional hotspots across class A GPCRs
Unifying view of mechanical and functional hotspots across class A GPCRs
G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of rec...
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Personal Name(s): | Ponzoni, Luca (Corresponding author) |
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Rossetti, Giulia (Corresponding author) / Maggi, Luca / Giorgetti, Alejandro / Carloni, Paolo / Micheletti, Cristian | |
Contributing Institute: |
Computational Biomedicine; IAS-5 JARA - HPC; JARA-HPC Jülich Supercomputing Center; JSC Computational Biomedicine; INM-9 Jara-Institut Quantum Information; INM-11 |
Published in: | PLoS Computational Biology, 13 (2017) 2, S. e1005381 - |
Imprint: |
San Francisco, Calif.
Public Library of Science
2017
|
DOI: |
10.1371/journal.pcbi.1005381 |
PubMed ID: |
28158180 |
Document Type: |
Journal Article |
Research Program: |
Towards the design of allosteric ligands binding to the human muscarinic receptor M2 Computational Science and Mathematical Methods Theory, modelling and simulation |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/13886 in citations.
G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors’ functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify those sites whose functional role is more clearly detected by considering dynamical and mechanical properties. Of these sites with a genuine mechanical/dynamical character, the top ranking is amino acid 7x52, a previously unexplored, and experimentally verifiable key site for GPCR conformational response to ligand binding. |