SUNY at Albany
June 19-23, 2001
Global and local deformability of DNA oligonucleotides
We report harmonic deformation potentials of selected DNA oligonucleotides on both global and base-pair step level. The results are based on a number of 5 ns unrestrained molecular dynamics simulations of 17-bp DNA duplexes with explicit inclusion of water and counterions. The oligonucleotides studied contain adenine, guanine, inosine (I), 5-methylcytosine, and 2-aminoadenine (D). The following sequences have been considered: homopolymers d(A)n, d(G) n, d(I) n, d(D) n, and alternating d(CpG) n, d(ApT) n, d(ApI) n. Inosine was paired with 5-methylcytosine.
The simulations were carried out using the AMBER package with both the Cornell et al. (1) and the new parm99 ( 2 )force fields. The elastic constants were derived by analyzing the correlations of fluctuations of structural properties along the trajectories [see Lankas et al.( 3 )for methodological details]. Particularly interesting is to study effects of base substitution on deformability. The I-metC base pair is sterically iso-structural with the A-T base pair while electrostatically it strongly resembles the G-C pair (4-6). On the other hand, the D-T base pair is sterically close to G-C while electrostatically similar to A-T. We are thus able to study the sterical and electostatic contributions to elastic properties independently. The results suggest that the stretching and twisting rigidities are determined by the presence of the amino group in the minor groove, while no clear rule has been observed in the case of isotropic bending rigidity. Structural aspects are discussed elsewhere (7).
On the local level, we calculated the harmonic force constants corresponding to the six base-pair step parameters (shift, slide, rise, tilt, roll, twist). Direct comparison with the deformabilities from protein-DNA crystal complexes (8) allows us to estimate the effective temperature of the crystallographic ensemble: 230K. We also investigated the dependence of the results on the helicoidal analysis algorithm used (9).
References and Footnotes
Filip Lankas (1), Jirí Sponer (1), Pavel Hobza (1), Jörg Langowski (2)
J. H. Insti of Phys. Chem.& Ctr for Complex Mole. Systems & Biomolecules(1)