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Albany 2001

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

Calculation of DNA Condensation Caused by Ligand Binding Using a Two-State Model

A theoretical method is developed for calculation of the DNA transition from linear to condensed state that is caused by binding of condensing ligands. We have presented before the one-state model for which abrupt condensation transition is caused by long-range interactions between all the ligands bound to DNA [D. Y. Lando, V. B. Teif, JBSD 18, 903-911 (2000)]. The two-state model considered here implies the existence of two states of a DNA molecule: linear (coil) state and condensed (globular) one. Ligand binding to different states of DNA molecules is characterized by different binding constants and stoichiometric parameters. Computation demonstrates that a small difference (less than 0.01√óRT per base pair) in the free energy of linear and condensed state is enough for existence of a stable linear state for free DNA molecule and stable condensed state after binding of condensing ions. The characteristics of condensation transition are very sensitive to the values of binding constants and stoichiometric parameters of ligand-DNA complexes.

A phenomenon of condensation at low ligand concentration and decondensation at high concentration found in experimental studies [Jary D., Sicorav J.-L., Biochemistry 38, 3223-3227 (1999)] may be explained using computer modeling for the two-state model. It was shown that decondensation follows the condensation during increase in ligand concentration if condensed state is energetically more favorable for ligand binding and the decondensed state is able to bind more ligands (per base pair) then the condensed one. In this case at very high ligand concentrations, decondensed state is entropically more favorable and an increase in ligand concentration gives rise to the decondensation.

This work was supported by Fund of Fundamental Investigations of the Republic of Belarus, Grant No X99R-099.

Vladimir B. Teif, Vladimir I. Vorob'ev and Dmitri Y. Lando

Institute of Bioorganic Chemistry, Belarus National Academy of Sciences, Kuprevich Str. 5/2, 220141 Minsk, Belarus. Email: Lando@ns.iboch.ac.by; Fax: 375-17-2648647; Phone: 375-17-2648263.
Institute of Cytology, Russian Academy of Sciences, Tikhoretsky prosp. 4, St. Petersburg 194064, Russia