Computational chemistry as a tool to understanding molecular level processes and designing `bio-inspired' materials

生物系统的分子水平特征是它们的多组分性质，丰富的高功能界面，以及它们固有的非平衡性。它们的分子构件是脂类、蛋白质、碳水化合物和核酸。在这项研究计划中，我们专注于蛋白质、脂类、光活性物质及其相互作用的理论和计算多尺度模型。我们集中在两个主题上：1)理解无序在蛋白质中的作用，2)玩弄光：使用计算化学和物理方法的光活性“生物启发”功能材料。这些计算机模拟提供了可以直接通过实验检验的定量预测。受生物启发的材料是人造或设计的材料，它使用有机/生物分子或结构作为构建块来实现所需的功能，例如对局部PH值的变化做出反应，与其他分子结合(或解离)，或收集光以获取能量。 上述过程受有机太阳能电池材料中分子水平的相互作用以及光的吸收和发射的控制。通过多尺度计算机模拟，我们的目标是确定那些驱动蛋白质-蛋白质相互作用等复杂过程及其后果的因素。这些信息随后将被应用于设计响应性材料。要研究的特殊情况包括蛋白质-蛋白质结合及其与细胞信号的联系，利用激光和来自分子包装的其他外部刺激释放药物，以及用于能量的光活性材料的设计。在细胞环境中，这些系统涉及与脂膜的相互作用。脂膜是对周围环境变化做出反应的功能性界面。膜还具有在不破坏其完整性的情况下融合的能力，这是将药物(和其他货物)输送到细胞中所必需的特性：脂膜是自然界最常见的纳米环境之一。 预期益处：上述知识对于自下而上的药物设计和仿生材料至关重要。这些都是快速发展的领域，根据我们以前的工作，我们在这些领域处于非常有利的地位。我们正在使用基础科学来提供加拿大工业，特别是中小型研发公司可以迅速利用的知识。因此，预计对这些问题及其应用的关注将推动加拿大成为这些领域的领导者。对于整个社会来说，这些调查的答案和应用具有深远的社会经济影响，因为它们是未来卫生保健材料的关键问题之一。作为一个直接的结果，新的计算方法和软件被期待。它们将作为开放源码免费提供给社区，以使加拿大和国外的研究人员受益。

The molecular level hallmarks of biological systems are their multicomponent nature, abundance of highly functional interfaces, and their inherent non-equilibrium nature. Their molecular building blocks are lipids, proteins, carbohydrates and nucleic acids. In this research program, we focus on theoretical and computational multiscale modelling of proteins, lipids, light-active materials and their interactions. We concentrate on two themes: 1) Understanding the role of disorder in proteins, and 2) Playing with light: Light-active 'bio-inspired' functional materials using methods of computational chemistry and physics. These computer simulations provide quantitative predictions that can be directly tested by experiments. Bio-inspired' materials are man-made or designed materials that use organic/biological molecules or structures as building blocks to achieve desired functionality, for example response to changes in local pH, binding to (& unbinding from) other molecules or harvesting light for energy. The above processes are controlled by molecular level interactions and absorption and emission of light in organic solar cell materials. With multiscale computer simulations, we aim to identify the ones that drive complex processes such as protein-protein interactions and their consequences. This information will then be applied to design responsive materials. Particular cases to be studied are protein-protein binding and its connection to cellular signalling, drug release using laser light and other external stimuli from molecular packing, and the design of photo-active materials for energy. In a cellular environment, these systems involve interactions with lipid membranes. Lipid membranes are functional interfaces that respond to changes in their surroundings. Membranes also possess the ability to fuse without losing their integrity, a property that is essential in drug (and other cargo) delivery into cells: the lipid membrane is one of nature's most common nano-environments. Anticipated benefits: The above knowledge is critical for bottom-up drug design and biomimetic materials. These are rapidly evolving fields in which, based on our previous work, we are extremely well-positioned. We are using basic science to provide knowledge that can be rapidly utilized by Canadian industries, especially small and medium sized R&D companies. It is thus anticipated that focusing on these questions and their applications will propel Canada as a leader in these fields. For society at large, the answers and applications resulting from these investigations are socio-economically far-reaching as they are among the key questions for health-care materials of future. As an immediate result, new computational methods and software are anticipated. They will be provided freely to the community as open source to benefit researchers both in Canada & abroad.