Encounter complexes and dimensionality reduction in protein-protein association
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Date
2014
Authors
Vajda, S.
Clore, G. M.
Paschalidis, Ioannis Ch.
Schueler-Furman, O.
Vakili, P.
Zheng, J.
Beglov, Dmitri
Hall, D.
Li, K.
Kozakov, D.
Version
OA Version
Citation
D Kozakov, K Li, D Hall, D Beglov, J Zheng, P Vakili, O Schueler-Furman, I Ch Paschalidis, GM Clore, S Vajda. 2014. "Encounter Complexes and Dimensionality Reduction in Protein-Protein Association." eLIFE, Volume 3:e01370,
Abstract
An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition.
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License
CC0 1.0 Universal
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.