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Deep mutational scanning: a new style of protein science

Abstract

Mutagenesis provides insight into proteins, but only recently have assays that couple genotype to phenotype been used to assess the activities of as many as 1 million mutant versions of a protein in a single experiment. This approach—'deep mutational scanning'—yields large-scale data sets that can reveal intrinsic protein properties, protein behavior within cells and the consequences of human genetic variation. Deep mutational scanning is transforming the study of proteins, but many challenges must be tackled for it to fulfill its promise.

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Figure 1: Deep mutational scanning generates large-scale mutational data.
Figure 2: Large-scale mutational data illustrate how protein sequence affects function.
Figure 3: Deep mutational scanning in sensitized backgrounds as a strategy for uncovering protein features.
Figure 4: Sequence-function maps of proteins important in disease.

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Acknowledgements

We thank A. Merz, M. Hochstrasser, C. Queitsch, A. Gitler, J. Bloom, E. Marcotte, E. Phizicky and M. Wickens for helpful discussions and comments. This work was supported by P41 GM103533 (to S.F.) and F32 GM084699 (to D.M.F.) from the US National Institute of General Medical Sciences. S.F. is supported by the Howard Hughes Medical Institute.

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Correspondence to Douglas M Fowler or Stanley Fields.

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Fowler, D., Fields, S. Deep mutational scanning: a new style of protein science. Nat Methods 11, 801–807 (2014). https://doi.org/10.1038/nmeth.3027

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