Cargando…
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 (...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239185/ https://www.ncbi.nlm.nih.gov/pubmed/21893589 http://dx.doi.org/10.1093/nar/gkr639 |
_version_ | 1782219138479947776 |
---|---|
author | Reshetnikov, Roman V. Sponer, Jiri Rassokhina, Olga I. Kopylov, Alexei M. Tsvetkov, Philipp O. Makarov, Alexander A. Golovin, Andrey V. |
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. |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3239185 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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. Nucleic Acids Res 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. |
spellingShingle | Structural Biology 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 |
title | 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_short | 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 |
topic | Structural Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3239185/ https://www.ncbi.nlm.nih.gov/pubmed/21893589 http://dx.doi.org/10.1093/nar/gkr639 |
work_keys_str_mv | AT reshetnikovromanv cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess AT sponerjiri cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess AT rassokhinaolgai cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess AT kopylovalexeim cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess AT tsvetkovphilippo cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess AT makarovalexandera cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess AT golovinandreyv cationbindingto15tbaquadruplexdnaisamultiplepathwaycationdependentprocess |