Conformational Flexibility of DNA sequences studied by Advanced
Molecular  Mechanics and Dynamics Tools

D 2003

Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools

FADRNÁ, Eva, Naděžda ŠPAČKOVÁ, Jiří ŠPONER and Jaroslav KOČA

Basic information

Original name

Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools

Authors

FADRNÁ, Eva (203 Czech Republic, guarantor), Naděžda ŠPAČKOVÁ (203 Czech Republic), Jiří ŠPONER (203 Czech Republic) and Jaroslav KOČA (203 Czech Republic)

Edition

2003. vyd. Praha, Book of Abstracts, p. 20-20, 2003

Publisher

Workshop on Modeling Interactions in Biomolecules

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

10403 Physical chemistry

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14310/03:00009170

Organization unit

Faculty of Science

Keywords in English

structure; dynamics; nucleic acids

Abstract

V originále

Molecular mechanics and dynamics is widely applied to various nucleic acids sequences in order to study their conformational behavior and flexibility. With increasing power of computational methods, it is possible to study structure-functional relationship in more detail. Wide range of methods has been applied to various G-DNA sequences that are able to form four-stranded arrangement. Taking part in controlling function of cells telomeras, these structures are in focus of biomolecular studies for more than 10 years. Computational methods contribute to the experimental ones and help them in prediction and explanation of structural features which can influence quadruplex formation, for example. Starting with conformational search of flexible parts of the molecule interesting conformational possibilities were found. Plain molecular dynamics as well as its modifications such as Locally Enhanced Sampling were used to study stability of geometries found by previous methods or described by experimental studies. Novel methods allow us to analyze the results in order to obtain free energy estimates. Some potential methodological pitfalls can be described by comparing free energy results and conformational preferences suggested for various structural sub-states. In contrast to experimentally observed results free energy analysis found different arrangement as the lowest energy one. Although the methods worked well until now, our results pointed out that still a lot of attention should be payed to methodological (force field) adjustments. Molecular dynamics is a powerful tool, but its routine use without careful attention to force field may be misleading. Anyway, our observations have shown big power of molecular dynamics and relative methods and pointed to potential course of the future methodological development.

Links

LN00A016, research and development project

Name: BIOMOLEKULÁRNÍ CENTRUM

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular Center

Citovat

FADRNÁ, Eva, Naděžda ŠPAČKOVÁ, Jiří ŠPONER and Jaroslav KOČA. Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools. In Book of Abstracts. 2003rd ed. Praha: Workshop on Modeling Interactions in Biomolecules, 2003, p. 20.

@inproceedings{490425,
   author = {Fadrná, Eva and Špačková, Naděžda and Šponer, Jiří and Koča, Jaroslav},
   address = {Praha},
   booktitle = {Book of Abstracts},
   edition = {2003},
   keywords = {structure; dynamics; nucleic acids},
   language = {eng},
   location = {Praha},
   pages = {20-20},
   publisher = {Workshop on Modeling Interactions in Biomolecules},
   title = {Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools},
   year = {2003}
}

TY  - JOUR
ID  - 490425
AU  - Fadrná, Eva - Špačková, Naděžda - Šponer, Jiří - Koča, Jaroslav
PY  - 2003
TI  - Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools
PB  - Workshop on Modeling Interactions in Biomolecules
CY  - Praha
KW  - structure
KW  - dynamics
KW  - nucleic acids
N2  - Molecular mechanics and dynamics is widely applied to various nucleic acids sequences in order to study their conformational behavior and flexibility. With increasing power of computational methods, it is possible to study structure-functional relationship in more detail. Wide range of methods has been applied to various G-DNA sequences that are able to form four-stranded arrangement. Taking part in controlling function of cells telomeras, these structures are in focus of biomolecular studies for more than 10 years. Computational methods contribute to the experimental ones and help them in prediction and explanation of structural features which can influence quadruplex formation, for example. Starting with conformational search of flexible parts of the molecule interesting conformational possibilities were found. Plain molecular dynamics as well as its modifications such as Locally Enhanced Sampling were used to study stability of geometries found by previous methods or described by experimental studies. Novel methods allow us to analyze the results in order to obtain free energy estimates. Some potential methodological pitfalls can be described by comparing free energy results and conformational preferences suggested for various structural sub-states. In contrast to experimentally observed results free energy analysis found different arrangement as the lowest energy one. Although the methods worked well until now, our results pointed out that still a lot of attention should be payed to methodological (force field) adjustments. Molecular dynamics is a powerful tool, but its routine use without careful attention to force field may be misleading. Anyway, our observations have shown big power of molecular dynamics and relative methods and pointed to potential course of the future methodological development.
ER  -

FADRNÁ, Eva, Naděžda ŠPAČKOVÁ, Jiří ŠPONER and Jaroslav KOČA. Conformational Flexibility of DNA sequences studied by Advanced Molecular Mechanics and Dynamics Tools. In \textit{Book of Abstracts}. 2003rd ed. Praha: Workshop on Modeling Interactions in Biomolecules, 2003, p.~20.

Detailed Information on Publication Record