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Dissecting protein structure and function using directed evolution

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To characterize the contributions of individual amino acids to the structure or function of a protein, researchers have adopted directed evolution approaches, which use iterated cycles of mutagenesis and selection or screening to search vast areas of sequence space for sets of mutations that provide insights into the protein of interest.

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Figure 1: A comparison of nonevolutionary and evolutionary approaches.
Figure 2: Sequence analysis and alanine scanning suggest a mechanism underlying the increased affinity of a mutant T-cell receptor16.

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Acknowledgements

We thank K. Esvelt for helpful discussions. C.M.Y. is supported by an Eli Lilly Organic Chemistry Graduate Fellowship. D.R.L. gratefully acknowledges support from the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Courtney M. Yuen and David R. Liu are at the Howard Hughes Medical Institute and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. drliu@fas.harvard.edu,

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Yuen, C., Liu, D. Dissecting protein structure and function using directed evolution. Nat Methods 4, 995–997 (2007). https://doi.org/10.1038/nmeth1207-995

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