Re-examination of the intrinsic, dynamic and hydration properties of phosphoramidate DNA.

Abstract:

:Intrinsic energetic and solvation factors contributing to the unusual structural and biochemical properties of N3'-phosphoramidate DNA analogs have been re-examined using a combination of quantum mechanical and molecular dynamics methods. Evaluation of the impact of the N3'-H substitution was performed via comparison of N3'-phosphoramidate DNA starting from both A- and B-form structures, B-form DNA and A-form RNA. The N3'-H group is shown to be flexible, undergoing reversible inversion transitions associated with motion of the hydrogen atom attached to the N3' atom. The inversion process is correlated with both sugar pucker characteristics as well as other local backbone torsional dynamics, yielding increased dihedral flexibility over DNA. Solvation of N3'-phosphoramidate DNA is shown to be similar to RNA, consistent with thermodynamic data on the two species. A previously unobserved intrinsic conformational perturbation caused by the N5'-phosphoramidate substitution is identified and suggested to be linked to the differences in the properties of N3'- and N5'-phosphoramidate oligonucleotide analogs.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Banavali NK,MacKerell AD

doi

10.1093/nar/29.15.3219

keywords:

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

3219-30

issue

15

eissn

0305-1048

issn

1362-4962

journal_volume

29

pub_type

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