Advances in the field of protein–protein docking allow us today to create models of protein complexes that approach in quality experimentally derived structures. Crucial to this is the explicit modelling of the conformational changes that the individual protein monomers undergo upon binding. A stringent energy function that allows the distinction between well-packed interfaces and wrong alternatives can then be used to select the correct model. The models can provide important insights into the biological function of the protein–protein interaction, and provide guidance to experimentalists. Thanks to their high resolution, these models are amenable to computational interface design methods that were until recently restricted to experimentally derived structures, thereby opening up the way towards docking-based redesign of interactions, or targeted inhibition. Nevertheless, proteins that undergo larger conformational changes upon binding are still difficult to model, but steady advances in this field allow for optimistic outlooks, even if challenges remain ahead.
|Original language||American English|
|Title of host publication||Protein-Protein Complexes|
|Subtitle of host publication||Analysis, Modeling and Drug Design|
|Publisher||Imperial College Press|
|Number of pages||27|
|State||Published - 1 Jan 2010|
Bibliographical noteFunding Information:
JJG is supported by the National Institutes of Health (grant K01-HG02316) and is a Beckman Young Investigator. I am grateful to Ora Schueler-Furman, George Rose and Arvind Sivasubramanian for providing thought-provoking comments on the manuscript. RosettaDock is available at rosettacommons.org, including full C++ source code, supporting scripts and documentation. Groups interested in contributing to the Rosetta project are encouraged to join the Commons.
© 2010 by Imperial College Press. All rights reserved.