Multiscale Theory and Simulation of Chemical Systems

化学系统的多尺度理论与模拟

• 批准号: RGPIN-2015-06594
• 负责人: Thachuk, Mark
• 金额: $ 1.46万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=614241
• 关键词: Multiscale; Theory; Simulation; Chemical; Systems

Many important questions in science involve phenomena acting upon varying length and time scales. For example, in biology, the binding of a ligand to a protein (atomistic event) can trigger changes in secondary and tertiary structure which then affect protein complex formation (mesoscopic event) which then affects biological activity in a cell (macroscopic event). This proposal seeks to utilize and develop multiscale modelling methods which can be used to answer questions involving disparate scales. This is broken down into three main themes. 1. Using coarse-grained or all-atom molecular dynamics techniques coupled with charge migration algorithms, the dissociation of gas phase protein complex ions will be studied.  Proof of concept simulations will explore the use of basic-site containing tethers to sequester charge in a complex, and create repulsive forces tailored at predefined positions, with the goal of producing site-directed dissociation forces.  The ability to dissociate a protein complex in a predefined manner will broaden immensely the experimental tools available for analyzing protein complex structure by mass spectrometry.  These methods require only commonly used chemical modifications of proteins.  With such methods, mass spectrometrists will be able to unlock the interactions in protein complexes and translate this back into biological function in cells. 2. The effect of nanoparticles on lipid vesicles will be investigated using a hybrid simulation methodology that treats some parts of a system atomistically, and other parts with a coarse-grained force field.  The hybrid method treats the two regions in a physically consistent way, while at the same time allowing detailed structural and even chemical effects to be described in areas of importance (the atomistic region).  There is intense interest in this problem due to health concerns over nanoparticle toxicity. 3. A method for correcting dynamical timescales in coarse-grained simulations will be explored in two ways.  First, by considering a system described completely with dissipative particle dynamics in which the necessary fluctuating forces are determined from atomistic molecular dynamics.  Second, by considering a hybrid method coupling an atomistic region treated with molecular dynamics with a mesoscopic region treated with dissipation particle dynamics.  In both cases, the result will be a coarse-grained description of the system fed by atomistic information for self-consistency.  A coarse-grained method with accurate dynamics can revolutionize simulation applications in a wide variety of fields, including materials science, biology, chemistry, and physics.

科学中的许多重要问题涉及对不同长度和时间尺度的现象。例如，在生物学中，配体与蛋白质（原子事件）的结合可以触发二级和三级结构的变化，然后影响蛋白质复合物的形成（介镜事件），然后影响细胞中的生物学活性（宏观事件）。该建议旨在利用和开发多尺度建模方法，这些方法可用于回答涉及不同尺度的问题。这将分为三个主要主题。 1。使用与电荷迁移算法结合的粗粒或全原子分子动力学技术，将研究气相蛋白质复合物离子的解离。概念验证模拟的证明将探索使用含有撕裂的基本地点以在复合体中隔离电荷的使用，并产生以预定义位置量身定制的排斥力，目的是产生定向位置的解离力。以预定义的方式分离蛋白质复合物的能力将扩大可用于通过质谱法分析蛋白质复合物结构的实验工具。这些方法仅需要常用的蛋白质化学修饰。通过这种方法，质谱学将能够解锁蛋白质复合物中的相互作用，并将其转换为细胞中的生物学功能。 2。将使用一种混合模拟方法研究纳米颗粒对脂质蔬菜的影响，该方法可将系统的某些部分和其他具有粗粒粒的力场处理。混合方法以身体一致的方式对待这两个区域，同时允许在重要性领域（原子区域）中描述详细的结构性甚至化学效应。由于对纳米颗粒毒性的健康问题，对这个问题引起了极大的兴趣。 3。将通过两种方式探讨一种在粗粒模拟中纠正动态时间尺度的方法。首先，通过考虑一个完全用耗散粒子动力学描述的系统，在该系统中，根据原子分子动力学确定必要的波动力。其次，通过考虑将用分子动力学处理的杂种方法与用耗散颗粒动力学处理的介观区处理的原子区域。在这两种情况下，结果都将是通过原子信息以自一矛而对系统进行粗粒的描述。具有准确动力学的粗粒方法可以彻底改变各种领域的模拟应用，包括材料科学，生物学，化学和物理学。