Abstract
Protein–protein interactions play critical roles in essentially every cellular process. These interactions are often mediated by protein interaction domains that enable proteins to recognize their interaction partners, often by binding to short peptide motifs. For example, PDZ domains, which are among the most common protein interaction domains in the human proteome, recognize specific linear peptide sequences that are often at the C-terminus of other proteins. Determining the set of peptide sequences that a protein interaction domain binds, or it’s “peptide specificity,” is crucial for understanding its cellular function, and predicting how mutations impact peptide specificity is important for elucidating the mechanisms underlying human diseases. Moreover, engineering novel cellular functions for synthetic biology applications, such as the biosynthesis of biofuels or drugs, requires the design of protein interaction specificity to avoid crosstalk with native metabolic and signaling pathways. The ability to accurately predict and design protein–peptide interaction specificity is therefore critical for understanding and engineering biological function. One approach that has recently been employed toward accomplishing this goal is computational protein design. This chapter provides an overview of recent methodological advances in computational protein design and highlights examples of how these advances can enable increased accuracy in predicting and designing peptide specificity.
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Ollikainen, N. (2017). Flexible Backbone Methods for Predicting and Designing Peptide Specificity. In: Schueler-Furman, O., London, N. (eds) Modeling Peptide-Protein Interactions. Methods in Molecular Biology, vol 1561. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6798-8_10
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DOI: https://doi.org/10.1007/978-1-4939-6798-8_10
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