Albany 2001

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

Conformational Dynamics of Nucleic Acids: Monte Carlo Sampling in the Space of Rigid Body and Sugar Pucker Variables

The JUMNA (Junction Minimization of Nucleic Acids) algorithm, originally developed for energy minimization and conformational search [1], has been extended to allowing for efficient conformational sampling. Local rigid body moves of the bases by three translations and three rotations and sugar re-puckering described by phase and amplitude [2] are combined with a new chain closure procedure. For each local move, a fast iterative solution of the non-linear chain closure equations yields the backbone and glycosidic torsion angles as dependent variables. Variations of exo-cyclic valence angles are included by minimizing a sum of harmonic energy terms. Only the lengths of covalent chemical bonds are fixed at their standard values.

Global changes of the structure evolve by applying the local moves to each nucleotide. In this way, low acceptance rates of Monte Carlo (MC) moves, as observed in internal-variable MC simulations [3], are avoided. The maximum step sizes adapted to a 50 % average acceptance rate at 300 K are in the order of 0.2Å for translations, 2º for rotations, 10º for sugar phases, 3º for sugar amplitudes, and 0.1º for endo-cyclic valence angles. Thus, short-lived conformational transitions, such as BI/BII transitions, a/g conversion, O4'-endo re-pucker, and more rarely C3'-endo re-pucker, are frequently observed events. In our first implementation of the method we used the standard Flex force field of JUMNA in combination with sigmoidal electrostatic damping. The usual reduction of phosphate charges, however, has been replaced by addition of explicit Na+ counter ions for electric neutrality. The performance of the simulations was tested by monitoring the equilibration of double-stranded DNA decamer structures starting from A- and B-conformations. Sequence-dependent conformational dynamics of the ten different di-nucleotide steps has been analyzed on the basis of converged production runs for the six periodic systems (A)n, (G)n , (AT)n , (GC)n , (GA)n , and (AC)n. Different conformations sampled during the MC trajectory are analyzed by using the CURVES algorithm which allows to visualize the dynamics by spectra of selected helicoidal and conformational variables. As far as possible, the results will be compared with experimental data.

Refrences and Footnotes
  1. R. Lavery, K. Zakrzewska and H. Sklenar, Comp. Phys. Comm. 1995, 91, 135-158
  2. H. A. Gabb, R. Lavery and C. Prevost, J. Comp. Chem. 1995, 16, 667-680
  3. H. A. Gabb, C. Prevost, G. Bertucat, C. H. Robert, and R. Lavery, J. Comp. Chem. 1997, 18, 2001-2011
  4. R. Lavery and H. Sklenar, J. Biomol. Struct. Dynam. 1989, 6, 655-667

Remo Rohs and Heinz Sklenar

Theoretical Biophysics Group, Max Delbruck Center for Molecular Medicine, Robert-Rossle-Str. 10, D-13092 Berlin, Germany
Phone: +49 30 9406 2561; Fax:+49 30 9406 2548; Email: sklenar@mdc-berlin.de