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Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation

The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies i...

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Autor principal: Monaco, Regina R.
Formato: Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925101/
https://www.ncbi.nlm.nih.gov/pubmed/20798766
http://dx.doi.org/10.4061/2010/702317
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author Monaco, Regina R.
author_facet Monaco, Regina R.
author_sort Monaco, Regina R.
collection PubMed
description The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies indicate that the creation of an intercalation site may occur spontaneously, with the energy for this interaction arising either from solvent collisions or soliton propagation along the helical axis. A subsequent 1D diffusional search by the ligand along the helical axis of the DNA will allow the ligand entry to this intercalation site from its external, electrostatically stabilized position. Other mechanistic studies show that ethidium cation participates in the creation of the site, as a ligand interacting closely with the external surface of the DNA can cause unfavorable steric interactions depending on the ligands' orientation, which are relaxed during the creation of an intercalation site. Briefly, such a site is created by the lengthening of the DNA molecule via bond rotation between the sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA itself and separation between the adjacent base pairs local to the position of the ligand, which becomes the intercalation site. Previous experimental measurements of this interaction measure the enthalpic cost of this part of the mechanism to be about −8 kcal/mol. This paper reports the observation, during a computational study, of the spontaneous opening of an intercalation site in response to the presence of a single ethidium cation molecule in an externally bound configuration. The concerted motions between this ligand and the host, a dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central …GATG… site was the intercalation site.
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spelling pubmed-29251012010-08-26 Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation Monaco, Regina R. J Nucleic Acids Research Article The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies indicate that the creation of an intercalation site may occur spontaneously, with the energy for this interaction arising either from solvent collisions or soliton propagation along the helical axis. A subsequent 1D diffusional search by the ligand along the helical axis of the DNA will allow the ligand entry to this intercalation site from its external, electrostatically stabilized position. Other mechanistic studies show that ethidium cation participates in the creation of the site, as a ligand interacting closely with the external surface of the DNA can cause unfavorable steric interactions depending on the ligands' orientation, which are relaxed during the creation of an intercalation site. Briefly, such a site is created by the lengthening of the DNA molecule via bond rotation between the sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA itself and separation between the adjacent base pairs local to the position of the ligand, which becomes the intercalation site. Previous experimental measurements of this interaction measure the enthalpic cost of this part of the mechanism to be about −8 kcal/mol. This paper reports the observation, during a computational study, of the spontaneous opening of an intercalation site in response to the presence of a single ethidium cation molecule in an externally bound configuration. The concerted motions between this ligand and the host, a dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central …GATG… site was the intercalation site. SAGE-Hindawi Access to Research 2010-03-31 /pmc/articles/PMC2925101/ /pubmed/20798766 http://dx.doi.org/10.4061/2010/702317 Text en Copyright © 2010 Regina R. Monaco. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Monaco, Regina R.
Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation
title Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation
title_full Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation
title_fullStr Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation
title_full_unstemmed Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation
title_short Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation
title_sort capture of a transition state using molecular dynamics: creation of an intercalation site in dsdna with ethidium cation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925101/
https://www.ncbi.nlm.nih.gov/pubmed/20798766
http://dx.doi.org/10.4061/2010/702317
work_keys_str_mv AT monacoreginar captureofatransitionstateusingmoleculardynamicscreationofanintercalationsiteindsdnawithethidiumcation