“Coarse Grained" Bead Modeling of Macromolecules Transport in Free Solution and in a Gel

The modeling of transport behavior of charged particles carried out in our laboratory is based on classical continuum electro kinetic theory. It is applied to a variety of systems from small electrolyte ions to macromolecules including peptides, DNA and nanoparticles. Systems range from weakly charged particles to highly charged ones. Transport properties studied include conductance, electrophoresis, and diffusion. In this dissertation, the conductance of polyvalent electrolytes ions is studied both by a “small ion” model [R.M. Fuoss, L. Onsager, J. Phys. Chem. 61 (1957) 668] and “large ion” model [R.W. O’Brien, L.R. White, J. Chem. Soc. Faraday Trans. 2 (74) (1978) 1607)]. Also, the coarse-grained continuum primitive model is developed and used to characterize the titration and electrical conductance behavior of aqueous solutions of fullerene hexa-malonic acid, which is a highly charged electrolyte with an absolute valence charge as high as 12. Free solution electrophoresis is closely related to conductance and a coarse-grained bead modeling methodology, BMM, developed in the Allison’s laboratory starting in 2006, is generalized to characterize peptide systems with respect to the charge, conformation, and possibly specific interactions with components of the BGE. For weakly charged peptides, the electrostatic potential is treated at the level of linear Poisson-Boltzmann equation, which predicts the electrophoretic mobility with considerable accuracy [S. Allison, H. Pei, U. Twahir, H. Wu, J. Sep. Sci., 2010, 33(16):2430-2438], but fails for highly charged systems. A new nonlinear Poisson-Boltzmann, NLPB-BM procedure is developed and applied to the free solution electrophoretic mobility of low molecular mass oligolysines. The difficulty of highly charged systems is twofold: more complex handeling of electrostatics and accounting for the relaxation effect. Both issues are addressed in this dissertation. A related problem we investigated deals with the retarding influence of a gel on the rotational motion of a macromolecule. This is investigated within the framework of the Effective Medium (EM) model and is applied to examine the electric birefringence decay of a 622 base pair DNA fragment in an agarose gel. Modeling is also compared with experiment. INDEX WORDS: Electrophoresis, Conductance, Diffusion, Coarse-Grained, Effective Medium, Relaxation Correction, Complex formation, Gel “COARSE GRAINED" BEAD MODELING OF MACROMOLECULES TRANSPORT IN FREE SOLUTION AND IN A GEL