Nucl._Acids_Res.-2003-Giudice-1434-43.pdf (409.04 kB)
Base pair opening within B-DNA: free energy pathways for GC and AT pairs from umbrella sampling simulations.
journal contribution
posted on 2023-06-08, 00:34 authored by Peter Varnai, Emmanuel Giudice, Richard LaveryThe conformational pathways and the free energy variations for base opening into the major and minor grooves of a B-DNA duplex are studied using umbrella sampling molecular dynamics simulations. We compare both GC and AT base pair opening within a double-stranded d(GAGAGAGAGAGAG). d(CTCTCTCTCTCTC) oligomer, and we are also able to study the impact of opening on the conformational and dynamic properties of DNA and on the surrounding solvent. The results indicate a two-stage opening process with an initial coupling of the movements of the bases within the perturbed base pair. Major and minor groove pathways are energetically comparable in the case of the pyrimidine bases, but the major groove pathway is favored for the larger purine bases. Base opening is coupled to changes in specific backbone dihedrals and certain helical distortions, including untwisting and bending, although all these effects are dependent on the particular base involved. Partial opening also leads to well defined water bridging sites, which may play a role in stabilizing the perturbed base pairs.
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- Published
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- Published version
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Nucleic Acids ResearchISSN
0305-1048External DOI
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5Volume
31Page range
1434-1443Department affiliated with
- Chemistry Publications
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- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-08-17Usage metrics
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