Free-Energy Profiles for A-/B-DNA Conformational Transitions in Isolated and Aggregated States from All-Atom Molecular Dynamics Simulation

Cheng Tsung Lai, George C Schatz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

In ordinary aqueous solution, B-DNA is the major structural form of DNA. After the addition of ethanol, DNA is thought to be aggregated/condensed in the A-form structure. However, there is uncertainty as to whether the B-To-A conformational change is connected to the aggregation/condensation steps. In this study, we performed all-Atom molecular dynamics simulations and calculated the free-energy surface involved in the A/B conformational transition for isolated and aggregated Dickerson-Drew dodecamers (DDDs) in water and 85% ethanol environments. We found in the case of an isolated DDD, the overall free-energy profile is entirely downhill to give the B-DNA conformation in both water and 85% ethanol. However, in the aggregated state and 85% ethanol environment, there is a free-energy minimum associated with the A-DNA region in addition to the global B-DNA minimum, and there is a â3 kcal/mol free-energy barrier to the A-To-B conformational change. The molecular dynamics results suggest that aggregation of DNA is essential for forming A-DNA.

Original languageEnglish
Pages (from-to)7990-7996
Number of pages7
JournalJournal of Physical Chemistry B
Volume122
Issue number33
DOIs
Publication statusPublished - Aug 23 2018

Fingerprint

B-Form DNA
Free energy
Molecular dynamics
DNA
Ethanol
A-Form DNA
deoxyribonucleic acid
free energy
molecular dynamics
Atoms
Computer simulation
profiles
atoms
ethyl alcohol
Agglomeration
simulation
Water
Energy barriers
Conformations
Condensation

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

@article{04bc73a206884dc0b71b7c7752301a8e,
title = "Free-Energy Profiles for A-/B-DNA Conformational Transitions in Isolated and Aggregated States from All-Atom Molecular Dynamics Simulation",
abstract = "In ordinary aqueous solution, B-DNA is the major structural form of DNA. After the addition of ethanol, DNA is thought to be aggregated/condensed in the A-form structure. However, there is uncertainty as to whether the B-To-A conformational change is connected to the aggregation/condensation steps. In this study, we performed all-Atom molecular dynamics simulations and calculated the free-energy surface involved in the A/B conformational transition for isolated and aggregated Dickerson-Drew dodecamers (DDDs) in water and 85{\%} ethanol environments. We found in the case of an isolated DDD, the overall free-energy profile is entirely downhill to give the B-DNA conformation in both water and 85{\%} ethanol. However, in the aggregated state and 85{\%} ethanol environment, there is a free-energy minimum associated with the A-DNA region in addition to the global B-DNA minimum, and there is a {\^a}3 kcal/mol free-energy barrier to the A-To-B conformational change. The molecular dynamics results suggest that aggregation of DNA is essential for forming A-DNA.",
author = "Lai, {Cheng Tsung} and Schatz, {George C}",
year = "2018",
month = "8",
day = "23",
doi = "10.1021/acs.jpcb.8b04573",
language = "English",
volume = "122",
pages = "7990--7996",
journal = "Journal of Physical Chemistry B",
issn = "1520-6106",
number = "33",

}

TY - JOUR

T1 - Free-Energy Profiles for A-/B-DNA Conformational Transitions in Isolated and Aggregated States from All-Atom Molecular Dynamics Simulation

AU - Lai, Cheng Tsung

AU - Schatz, George C

PY - 2018/8/23

Y1 - 2018/8/23

N2 - In ordinary aqueous solution, B-DNA is the major structural form of DNA. After the addition of ethanol, DNA is thought to be aggregated/condensed in the A-form structure. However, there is uncertainty as to whether the B-To-A conformational change is connected to the aggregation/condensation steps. In this study, we performed all-Atom molecular dynamics simulations and calculated the free-energy surface involved in the A/B conformational transition for isolated and aggregated Dickerson-Drew dodecamers (DDDs) in water and 85% ethanol environments. We found in the case of an isolated DDD, the overall free-energy profile is entirely downhill to give the B-DNA conformation in both water and 85% ethanol. However, in the aggregated state and 85% ethanol environment, there is a free-energy minimum associated with the A-DNA region in addition to the global B-DNA minimum, and there is a â3 kcal/mol free-energy barrier to the A-To-B conformational change. The molecular dynamics results suggest that aggregation of DNA is essential for forming A-DNA.

AB - In ordinary aqueous solution, B-DNA is the major structural form of DNA. After the addition of ethanol, DNA is thought to be aggregated/condensed in the A-form structure. However, there is uncertainty as to whether the B-To-A conformational change is connected to the aggregation/condensation steps. In this study, we performed all-Atom molecular dynamics simulations and calculated the free-energy surface involved in the A/B conformational transition for isolated and aggregated Dickerson-Drew dodecamers (DDDs) in water and 85% ethanol environments. We found in the case of an isolated DDD, the overall free-energy profile is entirely downhill to give the B-DNA conformation in both water and 85% ethanol. However, in the aggregated state and 85% ethanol environment, there is a free-energy minimum associated with the A-DNA region in addition to the global B-DNA minimum, and there is a â3 kcal/mol free-energy barrier to the A-To-B conformational change. The molecular dynamics results suggest that aggregation of DNA is essential for forming A-DNA.

UR - http://www.scopus.com/inward/record.url?scp=85052369613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052369613&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.8b04573

DO - 10.1021/acs.jpcb.8b04573

M3 - Article

VL - 122

SP - 7990

EP - 7996

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 33

ER -