Seminar: “Path sampling simulations of the mechanisms and rates of transitions between Watson-Crick and Hoogsteen base pairing in DNA”
on Friday the 11th of November there will be a IQTCUB seminar given by:
Jocelyne Vreede from the Van ‘t Hoff Institute for Molecular Sciences,
University of Amsterdam
entitled:
“Path sampling simulations of the mechanisms and rates of transitions
between Watson-Crick and Hoogsteen base pairing in DNA”
Time: 12:00
Place: Sala d’Actes, department of Physical Chemistry.
Abstract:
DNA duplexes predominantly contain Watson-Crick (WC) base pairs.
However, at any time, a non-negligible fraction of base pairs exhibit a
different interaction pattern, called Hoogsteen (HG) where the purine
base is rotated approximately 180° relative to its orientation in the WC
pairing. The conversion from WC to HG alters the conformation of DNA,
and may play a role in several processes, including recognition and
replication. The transient nature of these transitions hamper thorough
experimental investigation. Molecular dynamics simulations complement
experimental work by providing insights at very high spatial and
temporal resolution. Path sampling methods focus the molecular dynamics
effort on the dynamics during a transition, thus avoiding the long
waiting times in stable states. We apply two different path sampling
techniques to study the transitions between the WC and HG base pairing
motifs. By using transition path sampling we observed that the WC to HG
conversion can proceed along several mechanistic routes with varying
degrees of exposure of the purine. Employing transition interface
sampling, we computed the rates for this process, observing the same
trends as in experiment.