Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process

A combination of explicit solvent molecular dynamics simulation (30 simulations reaching 4 µs in total), hybrid quantum mechanics/molecular mechanics approach and isothermal titration calorimetry was used to investigate the atomistic picture of ion binding to 15-mer thrombin-binding quadruplex DNA (...

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Main Authors:	Reshetnikov, Roman V., Sponer, Jiri, Rassokhina, Olga I., Kopylov, Alexei M., Tsvetkov, Philipp O., Makarov, Alexander A., Golovin, Andrey V.
Format:	Online
Language:	English
Published:	Oxford University Press 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239185/

id	pubmed-3239185
recordtype	oai_dc
spelling	pubmed-32391852011-12-16 Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process Reshetnikov, Roman V. Sponer, Jiri Rassokhina, Olga I. Kopylov, Alexei M. Tsvetkov, Philipp O. Makarov, Alexander A. Golovin, Andrey V. Structural Biology A combination of explicit solvent molecular dynamics simulation (30 simulations reaching 4 µs in total), hybrid quantum mechanics/molecular mechanics approach and isothermal titration calorimetry was used to investigate the atomistic picture of ion binding to 15-mer thrombin-binding quadruplex DNA (G-DNA) aptamer. Binding of ions to G-DNA is complex multiple pathway process, which is strongly affected by the type of the cation. The individual ion-binding events are substantially modulated by the connecting loops of the aptamer, which play several roles. They stabilize the molecule during time periods when the bound ions are not present, they modulate the route of the ion into the stem and they also stabilize the internal ions by closing the gates through which the ions enter the quadruplex. Using our extensive simulations, we for the first time observed full spontaneous exchange of internal cation between quadruplex molecule and bulk solvent at atomistic resolution. The simulation suggests that expulsion of the internally bound ion is correlated with initial binding of the incoming ion. The incoming ion then readily replaces the bound ion while minimizing any destabilization of the solute molecule during the exchange. Oxford University Press 2011-12 2011-09-05 /pmc/articles/PMC3239185/ /pubmed/21893589 http://dx.doi.org/10.1093/nar/gkr639 Text en © The Author(s) 2011. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Reshetnikov, Roman V. Sponer, Jiri Rassokhina, Olga I. Kopylov, Alexei M. Tsvetkov, Philipp O. Makarov, Alexander A. Golovin, Andrey V.
spellingShingle	Reshetnikov, Roman V. Sponer, Jiri Rassokhina, Olga I. Kopylov, Alexei M. Tsvetkov, Philipp O. Makarov, Alexander A. Golovin, Andrey V. Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process
author_facet	Reshetnikov, Roman V. Sponer, Jiri Rassokhina, Olga I. Kopylov, Alexei M. Tsvetkov, Philipp O. Makarov, Alexander A. Golovin, Andrey V.
author_sort	Reshetnikov, Roman V.
title	Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process
title_short	Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process
title_full	Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process
title_fullStr	Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process
title_full_unstemmed	Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process
title_sort	cation binding to 15-tba quadruplex dna is a multiple-pathway cation-dependent process
description	A combination of explicit solvent molecular dynamics simulation (30 simulations reaching 4 µs in total), hybrid quantum mechanics/molecular mechanics approach and isothermal titration calorimetry was used to investigate the atomistic picture of ion binding to 15-mer thrombin-binding quadruplex DNA (G-DNA) aptamer. Binding of ions to G-DNA is complex multiple pathway process, which is strongly affected by the type of the cation. The individual ion-binding events are substantially modulated by the connecting loops of the aptamer, which play several roles. They stabilize the molecule during time periods when the bound ions are not present, they modulate the route of the ion into the stem and they also stabilize the internal ions by closing the gates through which the ions enter the quadruplex. Using our extensive simulations, we for the first time observed full spontaneous exchange of internal cation between quadruplex molecule and bulk solvent at atomistic resolution. The simulation suggests that expulsion of the internally bound ion is correlated with initial binding of the incoming ion. The incoming ion then readily replaces the bound ion while minimizing any destabilization of the solute molecule during the exchange.
publisher	Oxford University Press
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239185/
_version_	1611494551269146624

Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent process

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