P. Cieplak, T. E. Cheatham III, P. A. Kollman
Molecular dynamics simulations find that 3' phosphoramidate modified DNA duplexes undergo a B to A transition and normal DNA duplexes an A to B transition
We present unrestrained molecular dynamics studies on a deoxyribose dodecamer duplex d(CGCGAAT-TCGCG)(2) and its phosphoramidate
(replacing O3' by NH) analog using particle mesh Ewald electrostatics(1) and the Cornell et al. forte field.(2) The simulations were carried
out beginning in both canonical A and B forms, which differ in RMS position by similar to 6.5 Angstrom. These simulations, which were
carried out for similar to 1-1.5 ns, are consistent with experiment in that the unmodified dodecamer, whether started in A or B DNA,
converges to a B structure which is closer to the observed X-ray structure (9bna) than canonical B. On the other hand, the phosphoramidate
modified duplex, whether starred in A or B forms, converges to an A form. In this duplex, however, the structure from the simulation begun
in the Ii form has a dependence on the initial location of the N-H hydrogen. In one of our simulations, we find base pair opening and closing
at the end of the duplex. Specifically, in the simulation of d(CGCGAATTCGCG)(2) begun in the A form, base pair opening of the terminal
G-C base pair occurs at 400 ps, and then the bases remain unpaired for 700 ps before reclosing.
It evolved from its first time development slightly.
The dihedral part was developed based on HF/6-31g*
calculations for CH3-NH-PO2-OCH3 molecule
and by trying to reproduce rotation profile around N-P bond.
The NP-modified prep database
for DNA,RNA which could be used
for any modeling involving NP-modified polinucleotides,
which should work pretty well with any previous (not Weiner et al)
e.g. Cornell et al and post-Cornell et al databases.
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Fri Jun 29 17:44:33 BST 2001