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Future Med Chem. 2011 Mar;3(3):271-82. doi: 10.4155/fmc.10.289.

A combinatorial method to enable detailed investigation of protein-protein interactions.

Author information

1
The Institute of Structural & Molecular Biology, Research Department of Structural & Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK.

Abstract

BACKGROUND:

Successful structural investigations of protein-protein interactions can be facilitated by studying only the core interacting regions of the constituent proteins. However, attempting the discovery of stable core complexes using informed trial-and-error approaches can prove time and resource intensive.

METHODS:

We describe a valuable extension of combinatorial domain hunting (CDH), a technology for the timely elucidation of soluble protein truncations. The new method, CDH(2), enables empirical discovery of stable protein-protein core complexes. CDH(2) is demonstrated ab initio using a previously well-characterized Hsp90/Cdc37 complex.

RESULTS:

Without using a priori information, we demonstrate the isolation of stable protein-protein complexes, suitable for further analyses.

DISCUSSION:

This resource-efficient process can provide protein complexes for screening of compounds designed to modulate protein-protein interactions, thus facilitating novel drug discovery.

PMID:
21446842
DOI:
10.4155/fmc.10.289
[Indexed for MEDLINE]

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