DIMPLE: deep insertion, deletion, and missense mutation libraries for exploring protein variation in evolution, disease, and biology
Category
Published on
Type
journal-article
Author
Christian B. Macdonald and David Nedrud and Patrick Rockefeller Grimes and Donovan Trinidad and James S. Fraser and Willow Coyote-Maestas
Citation
Macdonald, C. B., Nedrud, D., Grimes, P. R., Trinidad, D., Fraser, J. S., & Coyote-Maestas, W. (2023). DIMPLE: deep insertion, deletion, and missense mutation libraries for exploring protein variation in evolution, disease, and biology. Genome Biology, 24(1). https://doi.org/10.1186/s13059-023-02880-6
Abstract
AbstractInsertions and deletions (indels) enable evolution and cause disease. Due to technical challenges, indels are left out of most mutational scans, limiting our understanding of them in disease, biology, and evolution. We develop a low cost and bias method, DIMPLE, for systematically generating deletions, insertions, and missense mutations in genes, which we test on a range of targets, including Kir2.1. We use DIMPLE to study how indels impact potassium channel structure, disease, and evolution. We find deletions are most disruptive overall, beta sheets are most sensitive to indels, and flexible loops are sensitive to deletions yet tolerate insertions.
