Atomistic insight into the kinetic pathways for Watson-Crick to Hoogsteen transitions in DNA.

Abstract:

:DNA predominantly contains Watson-Crick (WC) base pairs, but a non-negligible fraction of base pairs are in the Hoogsteen (HG) hydrogen bonding motif at any time. In HG, the purine is rotated ∼180° relative to the WC motif. The transitions between WC and HG may play a role in recognition and replication, but are difficult to investigate experimentally because they occur quickly, but only rarely. To gain insight into the mechanisms for this process, we performed transition path sampling simulations on a model nucleotide sequence in which an AT pair changes from WC to HG. This transition can occur in two ways, both starting with loss of hydrogen bonds in the base pair, followed by rotation around the glycosidic bond. In one route the adenine base converts from WC to HG geometry while remaining entirely within the double helix. The other route involves the adenine leaving the confines of the double helix and interacting with water. Our results indicate that this outside route is more probable. We used transition interface sampling to compute rate constants and relative free energies for the transitions between WC and HG. Our results agree with experiments, and provide highly detailed insights into the mechanisms of this important process.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Vreede J,Pérez de Alba Ortíz A,Bolhuis PG,Swenson DWH

doi

10.1093/nar/gkz837

subject

Has Abstract

pub_date

2019-12-02 00:00:00

pages

11069-11076

issue

21

eissn

0305-1048

issn

1362-4962

pii

5609526

journal_volume

47

pub_type

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