Exploring the essential collective dynamics of interacting proteins: application to prion protein dimers

  1. Get@NRC: Exploring the essential collective dynamics of interacting proteins: application to prion protein dimers (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1002/prot.24082
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Journal titleProteins: Structure, Function, and Bioinformatics
Pages18471865; # of pages: 19
Subjectprotein–protein interactions; flexibility; dynamic domains; correlated motions; binding free energy; molecular dynamics simulation; prion aggregation
AbstractEssential collective dynamics is a promising and robust approach for analysing the slow motions of macromolecules from short molecular dynamics trajectories. In this study, an extension of the method to treat a collection of interacting protein molecules is presented. The extension is applied to investigate the effects of dimerization on the collective dynamics of ovine prion protein molecules in two different arrangements. Examination of the structural plasticity shows that aggregation has a restricting effect on the local mobility of the prion protein molecules in the interfacial regions. Domain motions of the two dimeric ovine prion protein conformations are distinctly different and can be related to interatomic correlations at the interface. Correlated motions are among the slow collective modes extensively analysed by considering both main-chain and side-chain atoms. Correlation maps reveal the existence of a vast network of dynamically correlated side groups, which extends beyond individual subunits via interfacial interconnections. The network is formed by a core of hydrophobic side chains surrounded by hydrophilic groups at the periphery. The relevance of these findings are discussed in the context of mutations associated with prion diseases. The binding free energy of the dimeric conformations is evaluated to probe their thermodynamic stability. The descriptions afforded by the analysis of the essential collective dynamics of the prion dimers are consistent with their binding free energies. The agreement validates the extension of the methodology and provides a means of interpreting the collective dynamics in terms of the thermodynamic stability of ovine prion proteins.
Publication date
AffiliationSecurity and Disruptive Technologies; National Research Council Canada
NoteErratum published in Volume 80, Issue 9, page 2330, August 2012. Erratum DOI: 10.1002/prot.24139
Peer reviewedYes
NPARC number21268199
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Record identifierac6c61fe-0089-4aa1-aba0-96d9f7a1b72f
Record created2013-06-03
Record modified2016-05-09
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