Computational Studies of Ion Permeation and Polymer Translocation through Biological Channels

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Rob Coalson of the University of Pittsburgh is supported by the Theoretical and Computational Chemistry Program and the Molecular Biophysics Program to study fundamental aspects of the dynamics of ion permeation and biopolymer translocation in protein channels, using a variety of novel numerical and simulation methods. The three-dimensional Poisson-Nernst-Planck theory developed by the PI will be extended to include systematically a series of improvements on the description of ion and ion-solvent interactions. A Monte Carlo lattice-hopping model of ion permeation will also be explored, and results from both approaches will be compared. The related area of biopolymer translocation through protein channels will be investigated, exploring the effects of various levels of approximation. The advances in numerical solution procedures for computing simple ion currents and passage times for biopolymers that will result from this effort are expected to lead to software that enables computer aided design of protein channels with desired properties, such as large or rectified ion currents or enhanced chemical sensitivity for distinguishing DNA/RNA nucleotides.The permeation of ions and polymers through biological channels is an area characterized by important unanswered fundamental questions whose solution will have a direct and significant impact in medicine and biotechnology. By allowing ions to pass through otherwise impenetrable cell walls, protein channels contribute to the regulation of many physiological processes. They are blocked by toxins, degenerated by diseases, and stimulated by drugs. Therefore, an understanding of ion permeation is relevant to medical applications. It is also possible to flow strands of single stranded DNA and RNA through certain wide ion channels with an electric field, a property that may be exploited to generate chemical sensors with potential impacts in biotechnology.