Effects of induced polarisation on nanoscale behaviour of water and ions in ion channel pores and biomimetic nanopores

激发极化对离子通道孔和仿生纳米孔中水和离子纳米级行为的影响

基本信息

批准号：
2446176
负责人：
金额：
--
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2446176
关键词：
Effects induced polarisation nanoscale behaviour

项目摘要

Biological ion channels are integral to the healthy function of all living cells by allowing the selective permeation of ions and water across cell membranes to control cellular electrical activity and maintain cellular and ionichomeostasis. Their fundamental importance is highlighted by the number of diseases that result from ion channel dysfunction, as well as the range of therapeutic drugs that target the activity of ion channels and related proteins.Recent advances in membrane protein structural biology such as cryogenic electron microscopy and structure prediction with neural network-based models result in near exponential growth in the number of channel structuresbeing solved. Hence accurate methods for their functional annotation are needed. Determining molecular mechanisms which control permeation within these nanometer-scale pores is therefore critical for understandingtheir functional properties as well as for the development of new therapeutic strategies and future drug discovery. Computational simulation of channel structures is essential to understand these processes as it can be used to studythe behaviour of water and ions in channel pores to provide insights into their behaviour in such nanoconned spaces. Molecular dynamics (MD) simulations of channel pores are now widely used and have powerful predictivecapabilities. This DPhil project will use MD simulations with polarizable and nonpolarizable force fields to 1) study anion selectivity and binding free energies of ion carriers and tweezers, 2) study hydrophobic gates and the effect ofinduced polarization in ion channels and 3) perform large scale channel annotation using a fast-growing database of newly resolved structures.A research proposal submitted for the BBSRC Interdisciplinary Bioscience DTP at the University of Oxford. This work is relevant to the BBSRC Strategic Priority Areas of 'Systems Approaches to the Biosciences' and 'DataDriven Biology'.

生物离子通道是所有活细胞的健康功能不可或缺的一部分，它允许在细胞膜中选择性渗透离子和水，以控制细胞电活动并维持细胞和离子肉眼。 Their fundamental importance is highlighted by the number of diseases that result from ion channel dysfunction, as well as the range of therapeutic drugs that target the activity of ion channels and related proteins.Recent advances in membrane protein structural biology such as cryogenic electron microscopy and structure prediction with neural network-based models result in near exponential growth in the number of channel structuresbeing solved.因此，需要使用其功能注释的准确方法。因此，确定控制这些纳米尺寸孔内渗透的分子机制对于了解其功能性能以及新的治疗策略和未来药物发现的发展至关重要。通道结构的计算模拟对于理解这些过程至关重要，因为它可用于研究通道孔中的水和离子的行为，以洞悉其在这种纳米含量的空间中的行为。现在，通道孔的分子动力学（MD）模拟现在已被广泛使用，并且具有强大的预测性侵蚀性。该DPHIL项目将使用具有可极化和不可极化力场的MD模拟到1）研究阴离子的选择性和离子载体和镊子的结合自由能，2）研究疏水性门以及离子通道中诱导的极化的效果，以及3）使用新规模的供应数据库进行大规模研究的大规模研究，以实现大规模的渠道，以实现的范围供应研究BBBS，供应量的新型供应数据库。牛津大学的生物科学DTP。这项工作与BBSRC战略优先领域有关的“系统方法”和“ DataDriven Biology”。