Influence of BII Backbone Substates on DNA Twist: A Unified View and Comparison of Simulation and Experiment for All 136 Distinct Tetranucleotide Sequences

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F17%3A73583955" target="_blank" >RIV/61989592:15310/17:73583955 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/17:00477377 RIV/60461373:22310/17:43914586

Výsledek na webu

<a href="http://pubs.acs.org/doi/10.1021/acs.jcim.6b00621" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.jcim.6b00621</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.6b00621" target="_blank" >10.1021/acs.jcim.6b00621</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Influence of BII Backbone Substates on DNA Twist: A Unified View and Comparison of Simulation and Experiment for All 136 Distinct Tetranucleotide Sequences

Popis výsledku v původním jazyce

Reliable representation of the B-DNA base-pair step twist is one of the crucial requirements for theoretical modeling of DNA supercoiling and other biologically relevant phenomena in B-DNA. It has long been suspected that the twist is inaccurately described by current empirical force fields. Unfortunately, comparison of simulation results with experiments is not straightforward because of the presence of BII backbone substates, whose populations may differ in experimental and simulation ensembles. In this work, we provide a comprehensive view of the effect of BII substates on the overall B-DNA helix twist and show how to reliably compare twist values from experiment and simulation in two scenarios. First, for longer DNA segments freely moving in solution, we show that sequence averaged twists of different BI/BII ensembles can be compared directly because of approximate cancellation of the opposing BII effects. Second, for sequence-specific data, such as a particular base-pair step or tetranucleotide twist, can be compared only for a clearly defined BI/BII backbone conformation. For the purpose of force field testing, we designed a compact set of fourteen 22-base-pair B-DNA duplexes (Set 14) containing all 136 distinct tetranucleotide sequences and carried out a total of 84 mu s of molecular dynamics simulations, primarily with the OL15 force field. Our results show that the ff99bsc0 epsilon zeta(OL1 chi OL4), parmbscl, and OL15 force fields model the B-DNA helical twist in good agreement with X-ray and minicircle ligation experiments. The comprehensive understanding obtained regarding the effect of BEE substates on the base-pair step geometry should aid meaningful comparisons of various conformational ensembles in future research.

Název v anglickém jazyce

Influence of BII Backbone Substates on DNA Twist: A Unified View and Comparison of Simulation and Experiment for All 136 Distinct Tetranucleotide Sequences

Popis výsledku anglicky

Reliable representation of the B-DNA base-pair step twist is one of the crucial requirements for theoretical modeling of DNA supercoiling and other biologically relevant phenomena in B-DNA. It has long been suspected that the twist is inaccurately described by current empirical force fields. Unfortunately, comparison of simulation results with experiments is not straightforward because of the presence of BII backbone substates, whose populations may differ in experimental and simulation ensembles. In this work, we provide a comprehensive view of the effect of BII substates on the overall B-DNA helix twist and show how to reliably compare twist values from experiment and simulation in two scenarios. First, for longer DNA segments freely moving in solution, we show that sequence averaged twists of different BI/BII ensembles can be compared directly because of approximate cancellation of the opposing BII effects. Second, for sequence-specific data, such as a particular base-pair step or tetranucleotide twist, can be compared only for a clearly defined BI/BII backbone conformation. For the purpose of force field testing, we designed a compact set of fourteen 22-base-pair B-DNA duplexes (Set 14) containing all 136 distinct tetranucleotide sequences and carried out a total of 84 mu s of molecular dynamics simulations, primarily with the OL15 force field. Our results show that the ff99bsc0 epsilon zeta(OL1 chi OL4), parmbscl, and OL15 force fields model the B-DNA helical twist in good agreement with X-ray and minicircle ligation experiments. The comprehensive understanding obtained regarding the effect of BEE substates on the base-pair step geometry should aid meaningful comparisons of various conformational ensembles in future research.

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

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

—

Svazek periodika

57

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

275-287

Kód UT WoS článku

000395226100018

EID výsledku v databázi Scopus

2-s2.0-85014205547