Multiscale modeling of compounds and nanoparticles at liquid and soft matter interfaces

人们普遍认为，溶剂化对广泛的科学和技术至关重要。特别地，液体界面在化学、电化学、生物催化、生物学和药理学的各种技术应用中是至关重要的。在液体界面处，水溶剂和有机溶剂相遇并创造了一个具有独特性质的环境，这些性质可以进行微调以促进反应性和自组装。软物质纳米结构是通过竞争化学功能形成的复杂液体界面。一个重要的例子是活细胞和细胞内结构中生物膜的脂质双层。液体界面的结构和功能建模提出了一个挑战，这已被尝试在不同的复杂程度，从药物跨生物膜运输估计为散装液相之间的水和辛醇的分区，粗粒度的模拟纳米粒子易位跨脂质双层。 目前，有必要的溶剂化的理论模型，充分包括溶剂的分子结构，特别是在局部限制的化学和生物分子纳米系统和纳米材料。这样的理论模型是非常需要的，以扩展分子模拟的能力，这是远远不够的，以解决复杂的现象和过程的整个频谱的规模从快到非常慢的大型纳米系统的利益。基于统计力学的溶剂化理论模型可以是耦合到预测多尺度建模的所有部分的基本元素，包括化学结构和活性中心的量子描述，纳米结构的分子动力学（MD）和耗散粒子动力学（DPD），以及系统功能的粗粒模型。 基于统计力学第一原理的液体积分方程理论正变得越来越受欢迎，因为它提供了一个坚实的平台来处理溶液中复杂的化学和生物分子系统。特别是，3D-RISM-KH分子理论的溶剂化（三维参考相互作用网站模型与Kovalenko-Hirata封闭关系）已显示出大量的系统在解决方案中，否则不服从分子模拟或连续溶剂化处理的实质性成功。它已经发展到实用性的状态，并在多尺度方法学中与量子化学、MD和DPD模拟方法以及配体对接协议相结合，在主要软件包中实现的开发：阿姆斯特丹密度泛函（ADF）计算化学包、Amber MD包、AutoDock对接工具套件[9]和分子操作环境（莫伊）包。此外，现场现场推广的Lovett-Mou-Buff-Wertheim（SS-LMBW）积分微分方程构成的分子理论的液体界面，已被验证的非极性和复杂的缔合液体的平面界面。 该项目将把3D-RISM-KH和SS-LMBW方法结合在一个新的液体和软物质界面的精确分子理论中，并将其应用于复杂的化学和生物分子问题，包括：（i）功能化纳米颗粒在液体界面处的化学反应性，（ii）穿过生物膜和血脑屏障的药物转运，以及（iii）预测纳米颗粒穿过生物膜向不同尺寸和形状的纳米颗粒的纳米毒性数据库的移位，以及表面功能化。新的方法发展将被添加到莫伊（加拿大）和ADF（荷兰）软件包的现有实施中。三名博士生将参与并接受培训。

It is widely recognized that solvation is critical for a broad range of science and technology. In particular, liquid interfaces are of paramount importance in a variety of technological applications of chemistry, electrochemistry, biocatalysis, biology, and pharmacology. At liquid interfaces, aqueous and organic solvents meet and create an environment with unique properties that can be fine-tuned to promote reactivity and self-assembly. Soft matter nanostructures are complex liquid interfaces formed by competing chemical functionalities. An important example is a lipid bilayer of biomembranes in living cell and intracellular structures. Modeling structure and functions of liquid interfaces poses a challenge, which has been attempted at separate levels of complexity, from drug transport across a biomembrane estimated as partitioning between bulk liquid phases of water and octanol, to coarse-grained simulations of nanoparticle translocation across a lipid bilayer. At present, there is a need of theoretical models of solvation that adequately include molecular structure of solvent, in particular, in local confinement of chemical and biomolecular nanosystems and nanomaterials. Such theoretical models are of great demand to extend the capabilities of molecular simulations which are by far not sufficient to address complex phenomena and processes on the whole spectrum of scales from fast to very slow in large nanosystems of interest. Theoretical models of solvation based on statistical mechanics can be an essential element coupled to all parts of predictive multiscale modeling including quantum description for chemical structure and active centers, molecular dynamics (MD) and dissipative particle dynamics (DPD) for nanostructures, and coarse-grain models for system functions. Integral equation theory of liquids based on the first principles of statistical mechanics is becoming increasingly popular, as it provides a firm platform to handle complex chemical and biomolecular systems in solution. In particular, the 3D-RISM-KH molecular theory of solvation (three-dimensional reference interaction site model with the Kovalenko-Hirata closure relation) has shown substantial success for a number of systems in solution that otherwise were not amenable to molecular simulation or continuum solvation treatment. It has been advanced to the state of practical applicability and coupled in multiscale methodology with quantum chemistry, MD and DPD simulation methods, and ligand docking protocols, the developments implemented in major software packages: Amsterdam Density Functional (ADF) computational chemistry package, Amber MD package, AutoDock suite of docking tools [9], and Molecular Operating Environment (MOE) package. Furthermore, the site-site generalization of the Lovett-Mou-Buff-Wertheim (SS-LMBW) integro-differential equation constitutes a molecular theory of liquid interfaces which has been validated on planar interfaces of non-polar and complex associating liquids. This project will couple the 3D-RISM-KH and SS-LMBW approaches in a new accurate molecular theory of liquid nd soft matter interfaces, and will apply it to complex chemical and biomolecular problems, including: (i) chemical reactivity of functionalized nanoparticles at liquid interfaces, (ii) drug transport across biomembranes and the blood-brain barrier, and (iii) prediction of translocation of nanoparticles across biomembranes towards nanotoxicity database for nanoparticles of different size and shape, and surface functionalization. The new methodological developments will be added to the existing implementations in the MOE (Canada) and ADF (Netherlands) software packages. Three PhD students will be involved and trained in this project.