Multistate B- to A- Transition in Protein-DNA Binding - How Well is it Described by Current AMBER Force Fields?

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Multistate B- to A- Transition in Protein-DNA Binding - How Well is it Described by Current AMBER Force Fields?

Popis výsledku v původním jazyce

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 &lt; bsc1 &lt; 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.

Název v anglickém jazyce

Multistate B- to A- Transition in Protein-DNA Binding - How Well is it Described by Current AMBER Force Fields?

Popis výsledku anglicky

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 &lt; bsc1 &lt; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

<a href="/cs/project/GA20-28231S" target="_blank" >GA20-28231S: Komplexy protein-DNA a vývoj empirického potenciálu</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

JOURNAL OF BIOMOLECULAR STRUCTURE &amp; DYNAMICS

ISSN

0739-1102

e-ISSN

1538-0254

Svazek periodika

43

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

9017-9027

Kód UT WoS článku

001185638900001

EID výsledku v databázi Scopus

2-s2.0-85188439085