Article thumbnail

Encounter complexes and dimensionality reduction in protein-protein association

By S. Vajda, G. M. Clore, Ioannis Ch. Paschalidis, O. Schueler-Furman, P. Vakili, J. Zheng, D. Beglov, D. Hall, K. Li and D. Kozakov

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

Topics: FFT sampling, Encounter landscapes, Protein–protein interactions, Molecular docking simulation, Protein binding, Protein conformation, Proteins, Thermodynamics
Publisher: 'eLife Sciences Publications, Ltd'
Year: 2014
DOI identifier: 10.7554/eLife.01370.002
OAI identifier: oai:open.bu.edu:2144/18025

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles