Computational Studies of Ion Permeation and Polymer Translocation through Biological Channels

匹兹堡大学的Rob Coalson得到了理论和计算化学计划和分子生物物理计划的支持，利用各种新的数值和模拟方法研究蛋白质通道中离子渗透和生物聚合物转移动力学的基本方面。由PI发展的三维Poisson-Nernst-Planck理论将被扩展到系统地包括对离子和离子-溶剂相互作用的描述的一系列改进。还将探索离子渗透的蒙特卡罗晶格跳跃模型，并将两种方法的结果进行比较。生物聚合物通过蛋白质通道转运的相关领域将被调查，探索不同水平的近似的影响。这项工作将导致在计算生物聚合物的简单离子电流和通过时间的数值解方法方面的进展，有望导致能够使计算机辅助设计具有所需性质的蛋白质通道的软件，例如大的或整流的离子电流或增强的用于区分DNA/RNA核苷酸的化学敏感性。离子和聚合物通过生物通道的渗透是一个以重要的未解答的基本问题为特征的领域，其解决方案将对医学和生物技术产生直接和重大的影响。通过允许离子穿过原本无法穿透的细胞壁，蛋白质通道有助于调节许多生理过程。它们被毒素阻断，被疾病退化，被药物刺激。因此，了解离子渗透对医学应用具有重要意义。单链DNA和RNA也有可能在电场作用下流经某些宽阔的离子通道，这一特性可能被利用来产生在生物技术中具有潜在影响的化学传感器。

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.