Modeling the separation of macromolecules: a review of current computer simulation methods.

Theory and numerical simulations play a major role in the development of improved and novel separation methods. In some cases, computer simulations predict counterintuitive effects that must be taken into account in order to properly optimize a device. In other cases, simulations allow the scientist to focus on a subset of important system parameters. Occasionally, simulations even generate entirely new separation ideas! In this article, we review the main simulation methods that are currently being used to model separation techniques of interest to the readers of Electrophoresis. In the first part of the article, we provide a brief description of the numerical models themselves, starting with molecular methods and then moving towards more efficient coarse-grained approaches. In the second part, we briefly examine nine separation problems and some of the methods used to model them. We conclude with a short discussion of some notoriously hard-to-model separation problems and a description of some of the available simulation software packages.

Mesoscale modelling of polyelectrolyte electrophoresis.

The electrophoretic behaviour of flexible polyelectrolyte chains ranging from single monomers up to long fragments of a hundred repeat units is studied by a mesoscopic simulation approach. Abstracting from the atomistic details of the polyelectrolyte and the fluid, a coarse-grained molecular dynamics model connected to a mesoscopic fluid described by the Lattice-Boltzmann approach is used to investigate free-solution electrophoresis. Our study demonstrates the importance of hydrodynamic interactions for the electrophoretic motion of polyelectrolytes and quantifies the influence of surrounding ions. The length-dependence of the electrophoretic mobility can be understood by evaluating the scaling behavior of the effective charge and the effective friction. The perfect agreement of our results with experimental measurements shows that all chemical details and fluid structure can be safely neglected, and a suitable coarse-grained approach can yield an accurate description of the physics of the problem, provided that electrostatic and hydrodynamic interactions between all entities in the system, i.e., the polyelectrolyte, dissociated counterions, additional salt and the solvent, are properly accounted for. Our model is able to bridge the single molecule regime of a few nm up to macromolecules with contour lengths of more than 100 nm, a length scale that is currently not accessible to atomistic simulations.

Importance of hydrodynamic shielding for the dynamic behavior of short polyelectrolyte chains.

The dynamic behavior of polyelectrolyte chains in the oligomer range is investigated with coarse-grained molecular dynamics simulation and compared to data obtained by two different experimental methods, namely, capillary electrophoresis and electrophoresis NMR. We find excellent agreement of experiments and simulations when hydrodynamic interactions are accounted for in the simulations. We show that the electrophoretic mobility exhibits a maximum in the oligomer range and for the first time illustrate that this maximum is due to the hydrodynamical shielding between the chain monomers. Our findings demonstrate convincingly that it is possible to model dynamic behavior of polyelectrolytes using coarse-grained models for both the polyelectrolyte chains and the solvent induced hydrodynamic interactions.