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  • Perspective
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Toward high-resolution computational design of the structure and function of helical membrane proteins

Nature Structural & Molecular Biology volume 23, pages 475–480 (2016)Cite this article

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This Perspective provides an overview of the major advances in recent years in the computational design and structure prediction of α-helical membrane proteins.

Abstract

The computational design of α-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. Currently, the major hurdle for the field is the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress.

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Figure 1: Minimalistic active membrane designs.
Figure 2: Sequence and 3D contact motifs are strong predictors of local conformational stability.
Figure 3: Conformational membrane-protein thermostabilization by computational design.

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Acknowledgements

P.B. is supported by National Institutes of Health grant R01GM097207, by a Lilly Research Award Program and by a supercomputer allocation from XSEDE (MCB120101). A.S. is supported by National Institutes of Health grant R01GM0997522 and National Science Foundation grant CHE-1415910. We are grateful to S. Condon, S. Anderson, X. Feng and H. Cao for critical reading of the manuscript and to G. Grigoryan for providing the model of Rocker.

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Authors and Affiliations

  1. Structural and Computational Biology and Molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas, USA

    Patrick Barth

  2. Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA

    Patrick Barth

  3. Department of Pharmacology, Baylor College of Medicine, Houston, Texas, USA

    Patrick Barth

  4. Department of Biochemistry, University of Wisconsin–Madison, Madison, Wisconsin, USA

    Alessandro Senes

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Correspondence to Patrick Barth or Alessandro Senes.

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Barth, P., Senes, A. Toward high-resolution computational design of the structure and function of helical membrane proteins. Nat Struct Mol Biol 23, 475–480 (2016). https://doi.org/10.1038/nsmb.3231

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