Guanine base stacking in G-quadruplex nucleic acids
G-quadruplexes constitute a class of nucleic acid structures defined by stacked guanine tetrads (or G-tetrads) with guanine bases from neighboring tetrads stacking with one another within the G-tetrad core. Individual G-quadruplexes can also stack with one another at their G-tetrad interface leading...
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| Format: | Journal Article |
| Language: | English |
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2013
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| Online Access: | https://hdl.handle.net/10356/97174 http://hdl.handle.net/10220/9983 |
| _version_ | 1826121775750053888 |
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| author | Lech, Christopher Jacques Heddi, Brahim Phan, Anh Tuân |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Lech, Christopher Jacques Heddi, Brahim Phan, Anh Tuân |
| author_sort | Lech, Christopher Jacques |
| collection | NTU |
| description | G-quadruplexes constitute a class of nucleic acid structures defined by stacked guanine tetrads (or G-tetrads) with guanine bases from neighboring tetrads stacking with one another within the G-tetrad core. Individual G-quadruplexes can also stack with one another at their G-tetrad interface leading to higher-order structures as observed in telomeric repeat-containing DNA and RNA. In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures. A structural survey of the Protein Data Bank is conducted to characterize experimentally observed guanine base stacking geometries within the core of G-quadruplexes and at the interface between stacked G-quadruplex structures. We couple this survey with a systematic computational examination of stacked G-tetrad energy landscapes using quantum mechanical computations. Energy calculations of stacked G-tetrads reveal large energy differences of up to 12 kcal/mol between experimentally observed geometries at the interface of stacked G-quadruplexes. Energy landscapes are also computed using an AMBER molecular mechanics description of stacking energy and are shown to agree quite well with quantum mechanical calculated landscapes. Molecular dynamics simulations provide a structural explanation for the experimentally observed preference of parallel G-quadruplexes to stack in a 5′–5′ manner based on different accessible tetrad stacking modes at the stacking interfaces of 5′–5′ and 3′–3′ stacked G-quadruplexes. |
| first_indexed | 2024-10-01T05:38:01Z |
| format | Journal Article |
| id | ntu-10356/97174 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:38:01Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/971742023-02-28T19:40:12Z Guanine base stacking in G-quadruplex nucleic acids Lech, Christopher Jacques Heddi, Brahim Phan, Anh Tuân School of Physical and Mathematical Sciences DRNTU::Science::Physics::Atomic physics::Quantum theory G-quadruplexes constitute a class of nucleic acid structures defined by stacked guanine tetrads (or G-tetrads) with guanine bases from neighboring tetrads stacking with one another within the G-tetrad core. Individual G-quadruplexes can also stack with one another at their G-tetrad interface leading to higher-order structures as observed in telomeric repeat-containing DNA and RNA. In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures. A structural survey of the Protein Data Bank is conducted to characterize experimentally observed guanine base stacking geometries within the core of G-quadruplexes and at the interface between stacked G-quadruplex structures. We couple this survey with a systematic computational examination of stacked G-tetrad energy landscapes using quantum mechanical computations. Energy calculations of stacked G-tetrads reveal large energy differences of up to 12 kcal/mol between experimentally observed geometries at the interface of stacked G-quadruplexes. Energy landscapes are also computed using an AMBER molecular mechanics description of stacking energy and are shown to agree quite well with quantum mechanical calculated landscapes. Molecular dynamics simulations provide a structural explanation for the experimentally observed preference of parallel G-quadruplexes to stack in a 5′–5′ manner based on different accessible tetrad stacking modes at the stacking interfaces of 5′–5′ and 3′–3′ stacked G-quadruplexes. Published version 2013-05-23T08:00:17Z 2019-12-06T19:39:45Z 2013-05-23T08:00:17Z 2019-12-06T19:39:45Z 2012 2012 Journal Article Lech, C. J., Heddi, B., & Phan, A. T. (2013). Guanine base stacking in G-quadruplex nucleic acids. Nucleic Acids Research, 41(3), 2034-2046. https://hdl.handle.net/10356/97174 http://hdl.handle.net/10220/9983 10.1093/nar/gks1110 23268444 en Nucleic acids research © 2012 The Author(s). This paper was published in Nucleic Acids Research and is made available as an electronic reprint (preprint) with permission of The Author(s). The paper can be found at the following official DOI: [http://dx.doi.org/10.1093/nar/gks1110]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. application/pdf |
| spellingShingle | DRNTU::Science::Physics::Atomic physics::Quantum theory Lech, Christopher Jacques Heddi, Brahim Phan, Anh Tuân Guanine base stacking in G-quadruplex nucleic acids |
| title | Guanine base stacking in G-quadruplex nucleic acids |
| title_full | Guanine base stacking in G-quadruplex nucleic acids |
| title_fullStr | Guanine base stacking in G-quadruplex nucleic acids |
| title_full_unstemmed | Guanine base stacking in G-quadruplex nucleic acids |
| title_short | Guanine base stacking in G-quadruplex nucleic acids |
| title_sort | guanine base stacking in g quadruplex nucleic acids |
| topic | DRNTU::Science::Physics::Atomic physics::Quantum theory |
| url | https://hdl.handle.net/10356/97174 http://hdl.handle.net/10220/9983 |
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