Computational Design of Affinity and Specificity at Protein-Protein Interfaces

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Issue Date
2009-08Author
Karanicolas, John
Kuhlman, Brian
Publisher
Elsevier
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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The computer-based design of protein-protein interactions is a rigorous test of our understanding of molecular recognition and an attractive approach for creating novel tools for cell and molecular research. Considerable attention has been placed on redesigning the affinity and specificity of naturally occurring interactions. Several studies have shown that reducing the desolvation costs for binding while preserving shape complimentarity and hydrogen bonding is an effective strategy for improving binding affinities. In favorable cases specificity has been designed by focusing only on interactions with the target protein, while in cases with closely related off-target proteins, it has been necessary to explicitly disfavor unwanted binding partners. The rational design of protein-protein interactions from scratch is still an unsolved problem, but recent developments in flexible backbone design and energy functions hold promise for the future.
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Citation
Karanicolas, J., & Kuhlman, B. (2009). Computational Design of Affinity and Specificity at Protein-Protein Interfaces. Current Opinion in Structural Biology, 19(4), 458–463. http://doi.org/10.1016/j.sbi.2009.07.005
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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