Peptidic modulators of protein-protein interactions: Progress and challenges in computational design

Authors

  • Mor Rubinstein,

    1. The Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel
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  • Masha Y. Niv

    Corresponding author
    1. The Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel
    • The Institute of Biochemistry, Food Science and Nutrition, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel
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Abstract

With the decline in productivity of drug-development efforts, novel approaches to rational drug design are being introduced and developed. Naturally occurring and synthetic peptides are emerging as novel promising compounds that can specifically and efficiently modulate signaling pathways in vitro and in vivo. We describe sequence-based approaches that use peptides to mimic proteins in order to inhibit the interaction of the mimicked protein with its partners. We then discuss a structure-based approach, in which protein-peptide complex structures are used to rationally design and optimize peptidic inhibitors. We survey flexible peptide docking techniques and discuss current challenges and future directions in the rational design of peptidic inhibitors. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 505–513, 2009.

This article was originally published online as an accepted preprint. The “Published Online”date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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