Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00597520" target="_blank" >RIV/68081707:_____/24:00597520 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/24:73625496 RIV/61989100:27640/24:10255732 RIV/61989100:27740/24:10255732

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.4c00601" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.4c00601</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.4c00601" target="_blank" >10.1021/acs.jctc.4c00601</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes

Popis výsledku v původním jazyce

Mixed double helices formed by RNA and DNA strands, commonly referred to as hybrid duplexes or hybrids, are essential in biological processes like transcription and reverse transcription. They are also important for their applications in CRISPR gene editing and nanotechnology. Yet, despite their significance, the hybrid duplexes have been seldom modeled by atomistic molecular dynamics methodology, and there is no benchmark study systematically assessing the force-field performance. Here, we present an extensive benchmark study of polypurine tract (PPT) and Dickerson-Drew dodecamer hybrid duplexes using contemporary and commonly utilized pairwise additive and polarizable nucleic acid force fields. Our findings indicate that none of the available force-field choices accurately reproduces all the characteristic structural details of the hybrid duplexes. The AMBER force fields are unable to populate the C3 '-endo (north) pucker of the DNA strand and underestimate inclination. The CHARMM force field accurately describes the C3 '-endo pucker and inclination but shows base pair instability. The polarizable force fields struggle with accurately reproducing the helical parameters. Some force-field combinations even demonstrate a discernible conflict between the RNA and DNA parameters. In this work, we offer a candid assessment of the force-field performance for mixed DNA/RNA duplexes. We provide guidance on selecting utilizable force-field combinations and also highlight potential pitfalls and best practices for obtaining optimal performance.

Název v anglickém jazyce

Comprehensive Assessment of Force-Field Performance in Molecular Dynamics Simulations of DNA/RNA Hybrid Duplexes

Popis výsledku anglicky

Mixed double helices formed by RNA and DNA strands, commonly referred to as hybrid duplexes or hybrids, are essential in biological processes like transcription and reverse transcription. They are also important for their applications in CRISPR gene editing and nanotechnology. Yet, despite their significance, the hybrid duplexes have been seldom modeled by atomistic molecular dynamics methodology, and there is no benchmark study systematically assessing the force-field performance. Here, we present an extensive benchmark study of polypurine tract (PPT) and Dickerson-Drew dodecamer hybrid duplexes using contemporary and commonly utilized pairwise additive and polarizable nucleic acid force fields. Our findings indicate that none of the available force-field choices accurately reproduces all the characteristic structural details of the hybrid duplexes. The AMBER force fields are unable to populate the C3 '-endo (north) pucker of the DNA strand and underestimate inclination. The CHARMM force field accurately describes the C3 '-endo pucker and inclination but shows base pair instability. The polarizable force fields struggle with accurately reproducing the helical parameters. Some force-field combinations even demonstrate a discernible conflict between the RNA and DNA parameters. In this work, we offer a candid assessment of the force-field performance for mixed DNA/RNA duplexes. We provide guidance on selecting utilizable force-field combinations and also highlight potential pitfalls and best practices for obtaining optimal performance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

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

20

Číslo periodika v rámci svazku

15

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

6917-6929

Kód UT WoS článku

001270065500001

EID výsledku v databázi Scopus

2-s2.0-85198951698