Biophysical Properties of Tubulin and Microtubules and Their Nano-Biotechnology Potential

本项目的重点是植物和动物细胞中的关键蛋白质之一的生物物理特性：微管蛋白及其聚合形式微管。（聚合物是由重复亚基组合而成的分子结构。）来自不同物种（包括人类）的数百个微管蛋白基因已经被测序，这提供了大量关于微管蛋白结构和生物物理/生化特性的进化变化的未开发信息。我们打算在我们的研究中使用这些信息。我们将分析所有可用的微管蛋白序列，并基于蛋白质数据库中发现的已知微管蛋白模板构建蛋白质的3D模型。我们还将研究微管的一些生物物理性质，如静电荷及其空间分布。将研究已知与微管蛋白结合的关键药物的相互作用，以确定微管蛋白变体的特异性。这将使我们能够创建一个相互作用的地图，可以受到微管蛋白序列变化的影响，这是已知发生在不同的细胞类型中。在我们之前工作的基础上，我们将确定微管蛋白变体之间特定氨基酸的变化如何影响微管结构中相邻微管蛋白分子之间的结合亲和力。这将使我们了解微管的静态和动态力学性能，这些微管是由微管蛋白变体构成的。这些结果将填补现有关于微管蛋白结构-功能关系知识的空白。此外，我们计划继续研究微管的导电特性，与阿尔伯塔大学的尚卡尔小组合作，最终确定单个微管的电导、电容和可能的电感（这些是电学特性），这是由于微管周围的离子流造成的。我们打算扩展这种纳米尺度的实验，并将其与计算机建模相结合，以研究不同pH、离子浓度、温度变化和微管相关蛋白存在条件下的单个微管。在这里，我们计划量化这些影响，并包括1 kHz和1 MHz范围内的交流传导测量。这将使构建和表征复杂结构，如由蛋白质和蛋白质聚合物构建的微电路成为可能。这一目标的最终目标是为创造纳米生物电子元件和组合提供一个框架，以便在未来作为可生物降解和进化的计算设备应用。我们对这个项目的最终兴趣是模拟微管蛋白二聚体对几个范围内（kHz, MHz， GHz和THz）电磁频率的响应，以确定微管蛋白结构对这些领域的敏感性，包括基础和应用生物物理学方面的考虑。

This project is focused on the biophysical properties of one of the key proteins in plant and animal cells: tubulin and its polymerized form, microtubules. (Polymers are molecular structures that are assembled out of repeating subunits.)Hundreds of tubulin genes from various species (including human) have been sequenced, which provides an enormous amount of untapped information about evolutionary changes in the structure and the biophysical/biochemical properties of this protein. We intend to use this information in our study. We will analyze all available tubulin sequences and construct 3D models of the protein based on the known templates for tubulin found in the Protein Data Bank. We will also investigate several biophysical properties of microtubules such as electrostatic charges and their spatial distribution. The interactions of the key drugs known to bind to tubulin will be investigated for the specificity of tubulin variants. This will enable us to create a map of interactions that can be affected by variations in the sequences of tubulin, which are known to occur in different cell types. Building off our previous work we will determine how specific amino acid changes between variants of tubulin affect the binding affinity between neighbouring tubulin molecules in the microtubule structure. This will inform us about both the static and dynamic mechanical properties of microtubules constructed from variants of tubulin. These results will fill a gap in the existing knowledge about the structure-to-function relationship of tubulin.In addition, we plan to continue our investigations of the electric conduction properties of microtubules, in collaboration with the Shankar group at the University of Alberta, to conclusively determine single microtubule conductance, capacitance, and possibly inductance (these are electrical properties), due to ionic current flows around microtubules. We intend to extend this nano-scale experimentation and couple it with computer modeling to study individual microtubules under various conditions of pH, ionic concentrations, temperature variations, and the presence of microtubule-associated proteins. Here, we plan to quantify these effects and to include AC conduction measurements in the range between 1 kHz and 1 MHz. This will enable the construction and characterization of complex architectures intended as micro-circuitry built from proteins and protein polymers. The ultimate objective of this aim is to provide a framework for creating nano-bio-electronic elements and combinations, for application as biodegradable and evolvable computing devices in the future.Our final interest in this project is to simulate the response of tubulin dimers to electromagnetic frequencies in several ranges (kHz, MHz, GHz and THz), in order to determine the sensitivity of tubulin structure to these fields, both for basic and applied biophysics considerations.