Excessive aggregation of membrane proteins in the Martini model

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00482575" target="_blank" >RIV/61388963:_____/17:00482575 - isvavai.cz</a>

Result on the web

<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187936" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187936</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0187936" target="_blank" >10.1371/journal.pone.0187936</a>

Result language

angličtina

Original language name

Excessive aggregation of membrane proteins in the Martini model

Original language description

The coarse-grained Martini model is employed extensively to study membrane protein oligomerization. While this approach is exceptionally promising given its computational efficiency, it is alarming that a significant fraction of these studies demonstrate unrealistic protein clusters, whose formation is essentially an irreversible process. This suggests that the protein-protein interactions are exaggerated in the Martini model. If this held true, then it would limit the applicability of Martini to study multi-protein complexes, as the rapidly clustering proteins would not be able to properly sample the correct dimerization conformations. In this work we first demonstrate the excessive protein aggregation by comparing the dimerization free energies of helical transmembrane peptides obtained with the Martini model to those determined from FRET experiments. Second, we show that the predictions provided by the Martini model for the structures of transmembrane domain dimers are in poor agreement with the corresponding structures resolved using NMR. Next, we demonstrate that the first issue can be overcome by slightly scaling down the Martini protein-protein interactions in a manner, which does not interfere with the other Martini interaction parameters. By preventing excessive, irreversible, and non-selective aggregation of membrane proteins, this approach renders the consideration of lateral dynamics and protein-lipid interactions in crowded membranes by the Martini model more realistic. However, this adjusted model does not lead to an improvement in the predicted dimer structures. This implicates that the poor agreement between the Martini model and NMR structures cannot be cured by simply uniformly reducing the interactions between all protein beads. Instead, a careful amino-acid specific adjustment of the protein-protein interactions is likely required.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

<a href="/en/project/GBP208%2F12%2FG016" target="_blank" >GBP208/12/G016: Controlling structure and function of biomolecules at the molecular scale: theory meets experiment</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS ONE

ISSN

1932-6203

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

20

Pages from-to

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UT code for WoS article

000414997800031

EID of the result in the Scopus database

2-s2.0-85033687861