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

人们普遍认识到，溶剂化对广泛的科学技术至关重要。特别是，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都是至关重要的。在液体界面，水溶剂和有机溶剂相遇，创造了一个具有独特性质的环境，可以微调以促进反应性和自组装。软物质纳米结构是由相互竞争的化学功能形成的复杂的液体界面。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分子层。液体界面的结构和功能建模提出了一个挑战，这已经在不同的复杂性水平上进行了尝试，从估计为水和辛醇的散装液相之间的分配的生物膜上的药物运输，到脂质双分子层上纳米颗粒转运的粗粒度模拟。目前，在化学和生物分子纳米系统和纳米材料的局部约束中，需要充分包含溶剂分子结构的溶剂化理论模型。这样的理论模型对于扩展分子模拟的能力有很大的需求，到目前为止，分子模拟还不足以在整个范围内解决复杂的现象和过程，从快速到非常慢的大型纳米系统。基于统计力学的溶剂化理论模型可以成为预测多尺度建模所有部分的基本要素，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，为处理复杂的化学和生物分子系统提供了坚实的平台，正日益受到人们的欢迎。特别是，3D-RISM-KH分子溶剂化理论（具有kovalko - hirata闭合关系的三维参考相互作用位点模型）在溶液中的许多体系中取得了巨大的成功，否则这些体系不适合分子模拟或连续溶剂化处理。它已经发展到可实际应用的状态，并与量子化学、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了发展：阿姆斯特丹密度泛函数（ADF）计算化学软件包、Amber MD软件包、对接工具AutoDock套件[9]和分子操作环境（MOE）软件包。此外，对lovett - mu - bufff - wertheim （SS-LMBW）积分-微分方程的位-位推广构成了一种液体界面的分子理论，并在非极性和复杂缔合液体的平面界面上得到了验证。该项目将结合3D-RISM-KH和SS-LMBW方法，建立一种新的液体和软物质界面精确分子理论，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上的化学反应性，（ii）药物在生物膜和血脑屏障上的转运，以及（iii）纳米颗粒在生物膜上的易位预测，以建立不同尺寸和形状纳米颗粒的纳米毒性数据库，以及表面功能化。新的方法开发将被添加到MOE（加拿大）和ADF（荷兰）软件包中的现有实现中。本项目将有三名博士生参与并接受培训。

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.