Abstract
Computationally designed peptides targeting protein-protein interaction interfaces are of great interest as reagents for biological research and potential therapeutics. In recent years, it has been shown that detailed structure-based calculations can, in favorable cases, describe relevant determinants of protein-peptide recognition. Yet, despite large increases in available computing power, such accurate modeling of the binding reaction is still largely outside the realm of protein design. The chief limitation is in the large sequence spaces generally involved in protein design problems, such that it is typically infeasible to apply expensive modeling techniques to score each sequence. Toward addressing this issue, we have previously shown that by explicitly evaluating the scores of a relatively small number of sequences, it is possible to synthesize a direct mapping between sequences and scores, such that the entire sequence space can be analyzed extremely rapidly. The associated method, called Cluster Expansion, has been used in a number of studies to design binding affinity and specificity. In this chapter, we provide instructions and guidance for applying this technique in the context of designing protein-peptide interactions to enable the use of more detailed and expensive scoring approaches than is typically possible.
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Zheng, F., Grigoryan, G. (2017). Simplifying the Design of Protein-Peptide Interaction Specificity with Sequence-Based Representations of Atomistic Models. 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_11
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DOI: https://doi.org/10.1007/978-1-4939-6798-8_11
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