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Title: Prediction and validation of protein intermediate states from structurally rich ensembles and coarse grained simulations
Author: Orellana, Laura
Yoluk, Ozge
Carrillo, Oliver
Orozco López, Modesto
Lindhal, Erik
Keywords: Models moleculars
Molecular models
Issue Date: 31-Aug-2016
Publisher: Nature Publishing Group
Abstract: Protein conformational changes are at the heart of cell functions, from signalling to ion transport. However, the transient nature of the intermediates along transition pathways hampers their experimental detection, making the underlying mechanisms elusive. Here we retrieve dynamic information on the actual transition routes from principal component analysis (PCA) of structurally-rich ensembles and, in combination with coarse-grained simulations, explore the conformational landscapes of five well-studied proteins. Modelling them as elastic networks in a hybrid elastic-network Brownian dynamics simulation (eBDIMS), we generate trajectories connecting stable end-states that spontaneously sample the crystallographic motions, predicting the structures of known intermediates along the paths. We also show that the explored non-linear routes can delimit the lowest energy passages between end-states sampled by atomistic molecular dynamics. The integrative methodology presented here provides a powerful framework to extract and expand dynamic pathway information from the Protein Data Bank, as well as to validate sampling methods in general.
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It is part of: Nature Communications, 2016, vol. 7, p. 1-14
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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