Insights into Experimental Structures by Computational Models
While solution structures of adenine tract (A-tract) oligomers have indicated
a unique bend direction equivalent to negative global roll
(commonly termed ``minor-groove bending''),
crystallographic data have not unambiguously
characterized the bend direction;
nevertheless, many features are shared by all A-tract crystal
and solution structures
(e.g., propeller twisting, narrow minor grooves, and localized water spines).
To examine the origin of bending and to
relate findings to the crystallographic and solution data,
we analyze molecular dynamics trajectories of
two solvated A-tract dodecamers:
1D89, d(CGCGA6CG), and 1D98, d(CGCA6GCG),
using a new general global bending framework
for analyzing bent DNA and DNA/protein complexes.
It is significant that the crystallographically-based initial structures
are converted from dissimilar to similar bend directions
equivalent to negative global roll, with the average helical-axis bend
ranging from 10.5 º to 14.1 º.
The largest bend occurs as positive roll of 12 º
on the 5' side of the A-tracts
(supporting a junction model) and is reinforced by
gradual curvature at each A-tract base-pair (bp) step
(supporting a wedge model). The precise magnitude of the bend
is subtly sequence dependent (consistent with a curved general sequence model).
The conversion to negative global roll
only requires small local changes at each bp,
accumulated over flexible moieties both outside and inside the A-tract.
In contrast, the control sequence 1BNA, d(CGCGA2)TTCGCG),
bends marginally (only 6.9 º) with no preferred direction.
The molecular features that stabilize
the bend direction in the A-tract dodecamers
include propeller twisting of AT base-pairs, puckering differences
between A and T deoxyriboses, a narrow minor groove, and a stable water spine
(that extends slightly beyond the A-tract,
with lifetimes approaching 0.2 nanoseconds).
The sugar-conformations, in particular, are proposed
as important factors that support bent DNA.
It is significant that all these curvature-stabilizing features
are also observed in the crystallographic structures, but
yield overall different bending paths, largely due to the
effects of sequences outside the A-tract.
These results merge structural details reported for
A-tract structures by experiment and theory and
lead to structural and dynamic insights into sequence-dependent
DNA flexibility, as highlighted by the effect of
an A-tract variant of a TATA-box element on
bending and flexibility required for TBP binding.
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