Multistate B- to A- Transition in Protein-DNA Binding - How Well is it Described by Current AMBER Force Fields?
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F25%3A73630616" target="_blank" >RIV/61989592:15310/25:73630616 - isvavai.cz</a>
Result on the web
<a href="https://www.tandfonline.com/doi/epdf/10.1080/07391102.2024.2327539" target="_blank" >https://www.tandfonline.com/doi/epdf/10.1080/07391102.2024.2327539</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/07391102.2024.2327539" target="_blank" >10.1080/07391102.2024.2327539</a>
Alternative languages
Result language
angličtina
Original language name
Multistate B- to A- Transition in Protein-DNA Binding - How Well is it Described by Current AMBER Force Fields?
Original language description
When DNA interacts with a protein, its structure often undergoes a significant conformational adaptation, usually involving a transition from B-DNA towards the A-DNA form. This is not a two-state, but rather a multistate transition. The A- and B- forms differ mainly in sugar pucker (north/south) and glycosidic torsion χ (anti/high-anti). The combination of A-like pucker and B-like χ (and vice versa) represents the nature of the intermediate states between the pure A- and B- forms. Here we study how the A/B equilibrium and the A/B intermediate states at protein-DNA interfaces are modeled by current AMBER force fields. Eight diverse protein-DNA complexes and their naked (unbound) DNAs were simulated with OL15 and bsc1 force fields and an experimental combination OL15χOL3. We found that while the geometries of the A-like intermediate states agree well with the native X-ray geometries, their populations (stabilities) are significantly underestimated. Different force fields predict different propensities for A-like states growing in the order OL15 < bsc1 < OL15χOL3, yet all underestimate A-like form populations. Interestingly, the force fields seem to predict the correct sequence-dependent A-form propensity, as they predict larger populations of the A-like form in unbound DNA in those steps that acquire A-like conformations in protein-DNA complexes. The instability of A-like geometries in current force fields significantly alters the geometry of simulated protein-DNA complexes and destabilizes the binding motif, suggesting that refinement is required to improve description of protein-DNA interactions in AMBER force fields.
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
10610 - Biophysics
Result continuities
Project
<a href="/en/project/GA20-28231S" target="_blank" >GA20-28231S: Protein-DNA Complexes and Force Field Development</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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 BIOMOLECULAR STRUCTURE & DYNAMICS
ISSN
0739-1102
e-ISSN
1538-0254
Volume of the periodical
43
Issue of the periodical within the volume
16
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
9017-9027
UT code for WoS article
001185638900001
EID of the result in the Scopus database
2-s2.0-85188439085