Human telomeric G-DNA - a test example for force field adjustment

FADRNÁ, Eva, Naděžda ŠPAČKOVÁ, Daniel SVOZIL, Jiří ŠPONER and Jaroslav KOČA. Human telomeric G-DNA - a test example for force field adjustment. In Journal Of Biomolecular Structure and Dynamics. Albany: Adenine Press, 2007, p. 709-709. ISSN 0006-3525.

Basic information

• Original name: Human telomeric G-DNA - a test example for force field adjustment
• Name in Czech: Lidská telomerní G-DNA - testovací příklad pro vývoj silových polí
• Authors: FADRNÁ, Eva (203 Czech Republic, guarantor), Naděžda ŠPAČKOVÁ (203 Czech Republic), Daniel SVOZIL (203 Czech Republic), Jiří ŠPONER (203 Czech Republic) and Jaroslav KOČA (203 Czech Republic).
• Edition: Albany, Journal Of Biomolecular Structure and Dynamics, p. 709-709, 1 pp. 2007.
• Publisher: Adenine Press

Other information

• Original language: English
• Type of outcome: Proceedings paper
• Field of Study: 10403 Physical chemistry
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 2.389
• RIV identification code: RIV/00216224:14310/07:00022918
• Organization unit: Faculty of Science
• ISSN: 0006-3525
• UT WoS: 000247289600160
• Keywords in English: G-DNA; force field; human telomere
• Tags: force field, G-DNA, human telomere
• Tags: International impact

Abstract

Our interest has been focused on molecular modelling studies of DNA quadruplexes. Since these four-stranded arrangements play important role in cell cycle, they are currently extensively studied by means of experimental and computational techniques. Human telomeric sequence was extensively studied by means of molecular modelling tools. Starting from the X-ray structure we tested the influence of various ion types and radii on molecular dynamics, Locally Enhanced Sampling, free energy estimations, etc. Results have shown a strong influence of ion radius on conformational behavior during the trajectories. Greater computational force brings not only larger simulation timescale, but also cumulation of force-field imbalancies which can lead to some artifacts. Simple model of ion description influences entire potential energy surface and may shift the molecule from experimetal geometry. Slight changes in ion parameters force the simulation to completely different area of conformational space. Some (ir)reversible backbone changes of alpha-beta-gamma torsion angles (switches) have been observed in all trajectories that pointed out at some imbalancies in the force field parametrisation. Our study brought a contribution to some methodological tasks such as inclusions of proper ions type or backbone torsions switches. It has shown that human telomere sequence can be used as a testing example for recent methodological problems, because some imbalancies appear in it in relativelly short simulation time.

Abstract (in Czech)

Our interest has been focused on molecular modelling studies of DNA quadruplexes. Since these four-stranded arrangements play important role in cell cycle, they are currently extensively studied by means of experimental and computational techniques. Human telomeric sequence was extensively studied by means of molecular modelling tools. Starting from the X-ray structure we tested the influence of various ion types and radii on molecular dynamics, Locally Enhanced Sampling, free energy estimations, etc. Results have shown a strong influence of ion radius on conformational behavior during the trajectories. Greater computational force brings not only larger simulation timescale, but also cumulation of force-field imbalancies which can lead to some artifacts. Simple model of ion description influences entire potential energy surface and may shift the molecule from experimetal geometry. Slight changes in ion parameters force the simulation to completely different area of conformational space. Some (ir)reversible backbone changes of alpha-beta-gamma torsion angles (switches) have been observed in all trajectories that pointed out at some imbalancies in the force field parametrisation. Our study brought a contribution to some methodological tasks such as inclusions of proper ions type or backbone torsions switches. It has shown that human telomere sequence can be used as a testing example for recent methodological problems, because some imbalancies appear in it in relativelly short simulation time.

Links

• LC06030, research and development project: Name: Biomolekulární centrum

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

• MSM0021622413, plan (intention): Name: Proteiny v metabolismu a při interakci organismů s prostředím

Investor: Ministry of Education, Youth and Sports of the CR, Proteins in metabolism and interaction of organisms with the environment