Computational Studies of Ion Permeation and Polymer Translocation through Biological Channels

匹兹堡大学的Rob Coalson在理论与计算化学计划和分子生物物理学计划的支持下，使用各种新颖的数值和模拟方法，研究蛋白质通道中离子渗透和生物聚合物易位动力学的基本方面。由PI发展的三维泊松-能斯特-普朗克理论将被扩展到包括对离子和离子-溶剂相互作用描述的系统的一系列改进。我们还将探讨离子渗透的蒙特卡罗跳格模型，并比较两种方法的结果。通过蛋白质通道研究生物聚合物易位的相关领域，探索各种近似水平的影响。在计算简单离子电流和生物聚合物通过时间的数值解决程序方面的进步将由此产生，预计将导致软件能够使计算机辅助设计具有所需特性的蛋白质通道，例如大或整流离子电流或增强区分DNA/RNA核苷酸的化学灵敏度。离子和聚合物通过生物通道的渗透是一个具有重要未解基本问题的领域，其解决方案将对医学和生物技术产生直接和重大的影响。通过允许离子穿过难以穿透的细胞壁，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，对离子渗透的理解与医学应用有关。利用电场使单链DNA和RNA通过某些宽离子通道也是可能的，这一特性可能被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.