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PEDS Advance Access published online on July 2, 2009
Protein Engineering Design and Selection, doi:10.1093/protein/gzp032
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Review

Protein design in biological networks: from manipulating the input to modifying the output

Almer M. Van der Sloot1,3, Christina Kiel1, Luis Serrano1,2 and Francois Stricher1,3

1CRG-EMBL Systems Biology Program, Design of Biological Systems, Centre de Regulació Genòmica, Dr. Aiguader 88, 08003 Barcelona, Spain 2 Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain

3 To whom correspondence should be addressed. E-mail: francois.stricher{at}crg.es (F.S.)/almer.vandersloot{at}crg.es (A.M.V.S.)

Protein engineering has been an invaluable tool for the deciphering of protein folding and function and in the understanding of biological signaling networks. From an applied point of view it has been of paramount importance in biotechnological and biopharmaceutical products and applications. Traditionally, the protein engineering tools of choice were ‘classical’ rational design, or directed evolution-based methods. In recent years, a third tool has matured: computational protein design (CPD). In this review, we summarize the underlying principles of CPD and discuss its application for understanding and modifying biological systems. Three main applications of the use of protein design will be highlighted and reviewed: artificially rewiring of signal transduction networks, prediction and generation of large-scale in silico interaction networks and using protein design to manipulate gene expression.

Keywords: protein design/protein interaction networks/signaling/synthetic biology/systems biology

Received June 3, 2009; revised June 3, 2009; accepted June 7, 2009.


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