Predicting local geometric properties of DNA from
hydrodynamic diffusion data
Oscar Gonzalez
The sequence-dependent curvature and flexibility
of DNA is critical for its packaging into the cell,
recognition by other molecules, and conformational
changes during biochemically important processes.
However, few methods are available for directly
probing these properties at the basepair level.
In this talk, a model for estimating local
geometric properties of DNA from hydrodynamic
diffusion data on short sequences is described.
The model is based on a generalized conservation
of mass equation which describes the diffusional
dynamics of short DNA molecules in a dilute
solution. The coefficient matrix appearing in
this equation is defined through the solution of
the Stokes equations in the spatial domain
exterior to a single molecule. This coefficient
matrix provides a bridge between the microscopic
and macroscopic worlds. On one hand, this matrix
is completely determined by the microscopic
geometry of a hydrated molecule and can be
predicted by direct numerical solution of the
Stokes equations. On the other hand, certain
components of this matrix can be measured in
different types of macroscopic experiments. Thus
a model for exploring local geometric properties
of DNA is obtained. As an example application,
we use the model to predict the hydrated radius
of DNA under different assumptions on DNA
curvature. Our results indicate that previous
estimates of the radius, which were based on
an assumption of zero curvature, are likely to
be underestimates.
This is joint work with ICES PhD student J. Li.