Z-DNA as a Touchstone for Additive Empirical Force Fields and a Refinement of the Alpha/Gamma DNA Torsions for AMBER

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00554454" target="_blank" >RIV/68081707:_____/21:00554454 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/21:73609149

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.1c00697" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.1c00697</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.1c00697" target="_blank" >10.1021/acs.jctc.1c00697</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Z-DNA as a Touchstone for Additive Empirical Force Fields and a Refinement of the Alpha/Gamma DNA Torsions for AMBER

Popis výsledku v původním jazyce

Although current AMBER force fields are relatively accurate for canonical B-DNA, many noncanonical structures are still described incorrectly. As noncanonical motifs are attracting increasing attention due to the role they play in living organisms, further improvement is desirable. Here, we have chosen the Z-DNA molecule, which can be considered a touchstone of the universality of empirical force fields, since the noncanonical alpha and gamma backbone conformations native to Z-DNA are also found in protein-DNA complexes, i-motif DNA, and other noncanonical DNAs. We show that spurious alpha/gamma conformations occurring in simulations with current AMBER force fields, OL15 and bsc1, are largely due to inaccurate alpha/gamma parametrization. Moreover, stabilization of native Z-DNA substates involving gamma = trans conformations appears to be in conflict with the correct description of the canonical B-DNA structure. Because the balance of the native and spurious conformations is influenced by nonadditive effects, this is a difficult case for an additive dihedral energy scheme such as AMBER. We propose new alpha/gamma parameters, denoted OL21, and show that they improve the stability of native alpha/gamma Z-DNA substates while keeping the canonical DNA description virtually unchanged, thus representing a reasonable compromise within the additive force field framework. Although further extensive testing is needed, the new modification appears to be a promising step toward a more reliable description of noncanonical DNA motifs and provides the best performance for Z-DNA molecules among current AMBER force fields.

Název v anglickém jazyce

Z-DNA as a Touchstone for Additive Empirical Force Fields and a Refinement of the Alpha/Gamma DNA Torsions for AMBER

Popis výsledku anglicky

Although current AMBER force fields are relatively accurate for canonical B-DNA, many noncanonical structures are still described incorrectly. As noncanonical motifs are attracting increasing attention due to the role they play in living organisms, further improvement is desirable. Here, we have chosen the Z-DNA molecule, which can be considered a touchstone of the universality of empirical force fields, since the noncanonical alpha and gamma backbone conformations native to Z-DNA are also found in protein-DNA complexes, i-motif DNA, and other noncanonical DNAs. We show that spurious alpha/gamma conformations occurring in simulations with current AMBER force fields, OL15 and bsc1, are largely due to inaccurate alpha/gamma parametrization. Moreover, stabilization of native Z-DNA substates involving gamma = trans conformations appears to be in conflict with the correct description of the canonical B-DNA structure. Because the balance of the native and spurious conformations is influenced by nonadditive effects, this is a difficult case for an additive dihedral energy scheme such as AMBER. We propose new alpha/gamma parameters, denoted OL21, and show that they improve the stability of native alpha/gamma Z-DNA substates while keeping the canonical DNA description virtually unchanged, thus representing a reasonable compromise within the additive force field framework. Although further extensive testing is needed, the new modification appears to be a promising step toward a more reliable description of noncanonical DNA motifs and provides the best performance for Z-DNA molecules among current AMBER force fields.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GA17-16107S" target="_blank" >GA17-16107S: Konformační rovnováhy v nukleových kyselinách a vývoj empirického potenciálu</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

1549-9626

Svazek periodika

17

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

6292-6301

Kód UT WoS článku

000708673100023

EID výsledku v databázi Scopus

2-s2.0-85117180550