Multiscale Simulation of Phosphofructokinase-1 Assemblies: Capturing the Interplay between Specific and Transient Interactions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F25%3A00642022" target="_blank" >RIV/61388955:_____/25:00642022 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/full/10.1021/acs.jpcb.5c05346" target="_blank" >https://pubs.acs.org/doi/full/10.1021/acs.jpcb.5c05346</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jpcb.5c05346" target="_blank" >10.1021/acs.jpcb.5c05346</a>
Alternative languages
Result language
angličtina
Original language name
Multiscale Simulation of Phosphofructokinase-1 Assemblies: Capturing the Interplay between Specific and Transient Interactions
Original language description
Human phosphofructokinase-1 (PFK1) forms filaments and organizes into large-scale assemblies that are thought to play a key role in the spatial organization of glycolysis. However, the molecular interactions driving this assembly and the isoform-specific tendencies to form such structures remain poorly understood. In this work, we combine coarse-grained and all-atom molecular dynamics simulations to characterize interactions between PFK1 tetramers. Using the Martini and OPEPv7 coarse-grained force fields, we identify key regions mediating transient PFK1–PFK1 interactions and show that these include experimentally identified filament-forming interfaces. At the same time, we find that current coarse-grained models─optimized for nonspecific, transient contacts─lack the resolution to capture the specific side-chain interactions critical for filament stability, as revealed by previous experiments and our all-atom simulations. To address this, we propose enhancing the coarse-grained representation of filament-forming interfaces by introducing additional hydrogen-bonding terms for key residues. This modification improves filament stability and more accurately reproduces the effects of the filament-disrupting Asn-to-Thr mutation. Overall, our work provides a foundation for molecular-level modeling of glycolytic enzyme assemblies and offers a strategy to improve the accuracy of coarse-grained models in capturing the delicate interplay between specific and transient interactions in dynamic protein complexes.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
<a href="/en/project/GA23-06437S" target="_blank" >GA23-06437S: Allostery and spatial organization in glycolysis: the role of phosphofructokinase 1</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Physical Chemistry C
ISSN
1932-7447
e-ISSN
1932-7455
Volume of the periodical
129
Issue of the periodical within the volume
47
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
12098-12109
UT code for WoS article
001616529200001
EID of the result in the Scopus database
2-s2.0-105023177341