Dynamic protein interfaces and conformational landscapes of membrane protein complexes
•Dynamic membrane protein interfaces, in particular in GPCRs suggest novel regulatory and organizational paradigms.•Long timescale atomistic simulations give a glimpse of interactions between disordered binding regions.•Coarse-grain simulations are able to capture multiple binding modes of protein-p...
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| Published in: | Current opinion in structural biology Vol. 61; pp. 191 - 197 |
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| Main Authors: | , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Elsevier Ltd
01-04-2020
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| Online Access: | Get full text |
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| Summary: | •Dynamic membrane protein interfaces, in particular in GPCRs suggest novel regulatory and organizational paradigms.•Long timescale atomistic simulations give a glimpse of interactions between disordered binding regions.•Coarse-grain simulations are able to capture multiple binding modes of protein-protein interfaces.•Integrative coarse-grain and atomistic simulations with enhanced sampling techniques are the way forward.
Dynamic interactions between membrane proteins span a range of spatio-temporal scales and determine several cellular outcomes. Experimental methods in structure determination are able to resolve static protein–protein complexes at the membrane, but lack the resolution required for disordered, flexible domains and dynamic interactions. Computational approaches could bridge the resolution gap and help to unravel molecular details underlying these crucial interactions. Here, we review current approaches to predict dynamic membrane–protein complexes, with a focus on G protein-coupled receptors (GPCRs). Ensemble coarse-grain simulations have captured the conformational heterogeneity of several membrane receptor complexes. In conjunction, the conformational plasticity of protein interfaces especially encompassing unstructured domains is well represented by atomistic simulations. A combined integrative approach will pave the way forward to understand the molecular details of these dynamic complexes. |
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| Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
| ISSN: | 0959-440X 1879-033X |
| DOI: | 10.1016/j.sbi.2020.01.001 |