Albany 2001

category image Biomolecular
SUNY at Albany
June 19-23, 2001

Structure and dynamics of lateral loop regions of DNA guanine quadruplex d(G4T4G4)2 studied by advanced molecular modelling methods

It is well established that guanine rich sequences are able to form four stranded molecular assemblies = quadruplexes. Such structures are very important since their occurrence in genome of cells, for example human telomeras.

We have investigated an antiparallel DNA quadruplex formed by a dimerization of dGGGGTTTTGGGG with a four-tetrad stem and two lateral four-thymidine loop. Preceding explicit-solvent MD simulations [1,2] revealed that the stem of a quadruplex is an exceptionally rigid molecule. However, these studies also indicated large conformational plasticity of the four-thymidine loops which could not be fully captured even using multiple long simulations. In order to further explore the loop conformational space we have carried out a systematic conformational search of these loops using CICADA code [3,4]. Several interesting and previously unobserved loop geometries were found, often stabilized by asymmetric thymine base pairs. These geometries were further utilised as starting points in large-scale explicit solvent simulations and most of these geometries were apparently very stable. It confirms our preceding suggestion that the lateral G-DNA loops can adopt large number of nanosecond-scalestable geometries.

References and Footnotes
  1. N. Spackova, I. Berger and J. Sponer, J. Am. Chem. Soc. 121, 5519-5534 (1999).
  2. N. Spackova, I. Berger and J. Sponer, J. Am. Chem. Soc. 123 (2001) - in press
  3. J. Koca, J. Mol. Struct. (Theochem) 308, 13-24 (1994).
  4. E. Fadrna and J. Koca, J. Phys. Chem. B 101, 7863-7868 (1997).

Eva Fadrna (1), Nada Spackova (2), Jiri Sponer (2) and Jaroslav Koca (1)

(1) National Centre for Biomolecular Research, Faculty of Science, Masaryk University Brno, Kotlarska 2, 611 37 Brno, Czech Republic. Phone: +420-5-411 29 310. Fax: +420-5-411 29 506. E-mail: evaf@chemi.muni.cz , jkoca@chemi.muni.cz (2) Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, 612 65 Brno, Czech Republic.
Phone: +420-5-415 17 108. Fax: +420-5-412 112 93. E-mail: spackova@ibp.cz , sponer@ibp.cz