Effect of a neutralized phosphate backbone on the minor groove of B-DNA: molecular dynamics simulation studies

AUTOR(ES)

Hamelberg, Donald

FONTE

Oxford University Press

RESUMO

Alternative models have been presented to provide explanations for the sequence-dependent variation of the DNA minor groove width. In a structural model groove narrowing in A-tracts results from direct, short-range interactions among DNA bases. In an electrostatic model, the narrow minor groove of A-tracts is proposed to respond to sequence-dependent localization of water and cations. Molecular dynamics simulations on partially methylphosphonate substituted helical chains of d(TATAGGCCTATA) and d(CGCGAATTCGCG) duplexes have been carried out to help evaluate the effects of neutralizing DNA phosphate groups on the minor groove width. The results show that the time-average minor groove width of the GGCC duplex becomes significantly more narrow on neutralizing the phosphate backbone with methylphosphonates. The minor groove of the AATT sequence is normally narrow and the methylphosphonate substitutions have a smaller but measurable affect on this sequence. These results and models provide a system that can be tested by experiment and they support the hypothesis that the electrostatic environment around the minor groove affects the groove width in a sequence-dependent dynamic and time-average manner.

Documentos Relacionados

• Molecular dynamics simulation of the hydration shell of a B-DNA decamer reveals two main types of minor-groove hydration depending on groove width.
• A 5-nanosecond molecular dynamics trajectory for B-DNA: analysis of structure, motions, and solvation.
• A molecular dynamics simulation of double-helical B-DNA including counterions and water.
• Exocyclic groups in the minor groove influence the backbone conformation of DNA
• α/γ Transitions in the B-DNA backbone