2016
DOI: 10.1038/nsmb.3231
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Toward high-resolution computational design of the structure and function of helical membrane proteins

Abstract: The computational design of α-helical membrane proteins is still in its infancy but has made important progress. De novo design has produced stable, specific and active minimalistic oligomeric systems. Computational re-engineering can improve stability and modulate the function of natural membrane proteins. Currently, the major hurdle for the field is not computational, but the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress

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Cited by 33 publications
(32 citation statements)
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References 65 publications
(60 reference statements)
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“…Recently, Barth and coworkers demonstrated a successful transmembrane design (i.e. engineering) of a GPCR protein, which shows how a protein design algorithm may guide the alteration of transmembrane proteins affinity toward a certain ligand [89]. However, due to the complexity of transmembrane proteins as mentioned before, the design procedure was limited to rely mostly on homology modeling and ligand docking [90].…”
Section: The Scope Of Automated Protein Designmentioning
confidence: 99%
“…Recently, Barth and coworkers demonstrated a successful transmembrane design (i.e. engineering) of a GPCR protein, which shows how a protein design algorithm may guide the alteration of transmembrane proteins affinity toward a certain ligand [89]. However, due to the complexity of transmembrane proteins as mentioned before, the design procedure was limited to rely mostly on homology modeling and ligand docking [90].…”
Section: The Scope Of Automated Protein Designmentioning
confidence: 99%
“…In contrast to traditional synthetic biology approaches constructing new proteins from existing protein building blocks, more rational structure-based protein engineering strategies have emerged recently [5]. They enable the reprogramming of intrinsic receptor signaling functions and are not limited to receptors with modular architectures (Fig.…”
Section: Manipulating Receptor Signaling Through Design Of Intrinsmentioning
confidence: 99%
“…Consequently, the signaling properties of membrane receptors have remained challenging to engineer using rational protein engineering approaches. Recent progress in structure-based and rational membrane protein design techniques promise to expand the range of receptors and functions that can be redesigned [5]. Meanwhile, empirical synthetic biology approaches have exploited the modularity of few membrane protein families for creating synthetic chimeric receptors to redirect cellular signaling, and some have been successfully translated to clinical application in engineered cell therapies [6].…”
Section: Introductionmentioning
confidence: 99%
“…without being limited to the set of naturally-occurring oligomers. Previous homo-oligomer design efforts have focused primarily on all a-proteins with nonglobular structures such as coiled coils [7][8][9][10][11][12][13][14] and repeat proteins, 15 and disulfide-linked oligomers. [16][17][18][19] Compared to oligomers made from elongated helical bundles, homo-oligomeric structures made from globular building blocks have the advantage of multiple reconfigurable interfaces associated with subunit rotations along multiple axes.…”
Section: Introductionmentioning
confidence: 99%