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A multidisciplinary approach for the computational assembly of large molecular machines from electron density maps

Ziel

Proteins are often organized in large, dynamic molecular machines. A mechanistic, atomic-resolution understanding of these machines would provide fundamental insights into the clockwork of the complex machinery underlying human life. However, machines such as the 26S-proteasome have resisted crystallization attempts for decades.
Cryo-electron microscopy (cryo-EM) has provided insightful maps of molecular machines, but these lack atomic resolution. In principle, molecular machines can be assembled from atomic homology models of the subunits. However, homology models often contain large errors, causing existing assembly methods to fail.
Here I present a multidisciplinary approach for the assembly of large molecular machines from cryo-EM maps. I will combine computational techniques from cryo-EM, homology modelling and interface prediction into ATTRACT, the only docking method that integrates subunit flexibility into the initial search. Driven by a cryo-EM density map, ATTRACT’s coordinated motions will reduce the initial homology model errors, bending the subunits into the correct shape while they are being assembled.
The challenging nature of the problem requires the integration of approaches. After firm assessment of the abilities of the method, it will be applied to experimental density maps of the proteasome and other molecular machines, providing new fundamental insights when neither complex nor subunits are known.

Wissenschaftliches Gebiet (EuroSciVoc)

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Thema/Themen

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2010-IEF
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IEF - Intra-European Fellowships (IEF)

Koordinator

TECHNISCHE UNIVERSITAET MUENCHEN
EU-Beitrag
€ 162 242,40
Adresse
Arcisstrasse 21
80333 Muenchen
Deutschland
Region
Bayern Oberbayern München, Kreisfreie Stadt
Aktivitätstyp
Higher or Secondary Education Establishments
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