Deep mutational scanning: a new style of protein science

• Published in: Nature methods Vol. 11; no. 8; pp. 801 - 807
• Main Authors: Fowler, Douglas M, Fields, Stanley
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2014; Nature Publishing Group
• Subjects: 45; 45/47; 49; 631/114/663; 631/1647/2163; 631/208/737; 631/45/612; 82; 82/47; Bioinformatics; Biological Microscopy; Biological Techniques; Biomedical Engineering/Biotechnology; Gene mutations; Genetic diversity; Genetic Variation; Humans; Identification and classification; Life Sciences; Mutation; perspective; Protein Engineering; Protein research; Proteins; Proteins - chemistry; Proteins - genetics; Proteomics; Science
• ISSN: 1548-7091; 1548-7105
• DOI: 10.1038/nmeth.3027

This Perspective discusses the power of large mutational scans for the study of protein properties, the analytical challenges posed by the resulting data sets and the potential of this approach to further our understanding of human genetic variation. 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.