Book of Abstracts: Albany 2007
June 19-23 2007
Human telomeric G-DNA ? a test example for force field adjustment
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 been shown that human telomere sequence can be used as a testing example for recent methodological problems, because some imbalances appear in it in relativelly short simulation time.
1National Centre for Biomolecular Research, Faculty of Science, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic. Phone: +420-5-4949 3716. Fax: +420-5-4949 2556. E-mail: firstname.lastname@example.org , email@example.com