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Modeling Peptide-Protein Structure and Binding Using Monte Carlo Sampling Approaches: Rosetta FlexPepDock and FlexPepBind

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Modeling Peptide-Protein Interactions

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1561))

Abstract

Many signaling and regulatory processes involve peptide-mediated protein interactions, i.e., the binding of a short stretch in one protein to a domain in its partner. Computational tools that generate accurate models of peptide-receptor structures and binding improve characterization and manipulation of known interactions, help to discover yet unknown peptide-protein interactions and networks, and bring into reach the design of peptide-based drugs for targeting specific systems of medical interest.

Here, we present a concise overview of the Rosetta FlexPepDock protocol and its derivatives that we have developed for the structure-based characterization of peptide-protein binding. Rosetta FlexPepDock was built to generate precise models of protein-peptide complex structures, by effectively addressing the challenge of the considerable conformational flexibility of the peptide. Rosetta FlexPepBind is an extension of this protocol that allows characterizing peptide-binding affinities and specificities of various biological systems, based on the structural models generated by Rosetta FlexPepDock. We provide detailed descriptions and guidelines for the usage of these protocols, and on a specific example, we highlight the variety of different challenges that can be met and the questions that can be answered with Rosetta FlexPepDock.

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Authors and Affiliations

  1. Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hadassah Medical School, The Hebrew University of Jerusalem, 12272, Jerusalem, 91120, Israel

    Nawsad Alam & Ora Schueler-Furman

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  1. Nawsad Alam
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  2. Ora Schueler-Furman
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Correspondence to Ora Schueler-Furman .

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Editors and Affiliations

  1. Microbiology and Molecular Genetics, Hebrew University Hadassah Medical School, Jerusalem, Israel

    Ora Schueler-Furman

  2. Organic Chemistry, The Weizmann Institute of Science, Rehovot, Israel

    Nir London

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Alam, N., Schueler-Furman, O. (2017). Modeling Peptide-Protein Structure and Binding Using Monte Carlo Sampling Approaches: Rosetta FlexPepDock and FlexPepBind. 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_9

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