Institute of Organic Chemistry and Biochemistry
Flemingovo nam. 2
166 10 Praha 6
F. Lankas, T.E. Cheatham III, N. Spackova, P. Hobza, J. Langowski, J. Sponer
Biophys. J. 2002 82:2592-2609
Critical effect of the N2 amino group on structure, dynamics, and elasticity
of DNA polypurine tracts
Unrestrained 5-20-ns explicit-solvent molecular dynamics simulations using the Cornell et al. force field have been carried out for d[GCG(N)11GCG]2 (N, purine base) considering guanine·cytosine (G·C), adenine·thymine (A·T), inosine·5-methyl-cytosine (I·mC), and 2-amino-adenine·thymine (D·T) basepairs. The simulations unambiguously show that the structure and elasticity of N-tracts is primarily determined by the presence of the aminogroup in the minor groove. Simulated A-, I-, and AI-tracts show almost identical structures, with high propeller twist and minor groove narrowing. G- and D-tracts have small propeller twisting and are partly shifted toward the A-form. The elastic properties also differ between the two groups. The sequence-dependent electrostatic component of base stacking seems to play a minor role. Our conclusions are entirely consistent with available experimental data. Nevertheless, the propeller twist and helical twist in the simulated A-tract appear to be underestimated compared to crystallographic studies. To obtain further insight into the possible force field deficiencies, additional multiple simulations have been made for d(A)10, systematically comparing four major force fields currently used in DNA simulations and utilizing B and A-DNA forms as the starting structure. This comparison shows that the conclusions of the present work are not influenced by the force field choice.
This is a contributed parameter set for D-5-METHYL-CYTOSINE
with 5'-phosphate group and 3'-O(minus) group,
to be used with the AMBER parmbsc0 force field.
The following bonded parameters were missing in the parmbsc0 force field:
CA-CM-CT corresponding to the angle C4-C5-C7
They were replaced by analogous parmbsc0 parameters:
C-CM-CT in analogy with the thymine angle C4-C5-C
The charges were computed using a standard RESP procedure.
The parameters were obtained by Filip Lankas and Tomas Drsata.
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17 Sep 2012