Modeling the sequence-dependent diffusion coefficients of short DNA molecules.

A boundary element model for the computation of sequence-dependent hydrodynamic properties of short DNA molecules is introduced. The hydrated surface is modeled as a curved tube of uniform radius with ends capped by hemispheres, and the axis of the tube is a general space curve whose length and curvature are determined locally by the sequence using a rigid basepair model of double-helical DNA with parameters based on x-ray crystallography. Diffusion coefficients for families of random and periodic DNA sequences are computed and compared with theories for straight tubes and experimental data. Our results indicate that sequence-dependent curvature can have a measurable impact on both the translational and rotational diffusion coefficients, even for relatively short fragments of lengths less than about 150 basepairs, and that previous estimates of the hydrated radius of DNA are likely to be underestimates. Moreover, our results suggest a possible method for refining the rigid basepair model parameters for DNA in solution as well as the hydrated radius.