Multiscale modeling of liquid interfacial phases in biomolecular environments and nanomaterials

人们普遍认为，溶剂化对于广泛的科学和技术是至关重要的。特别是，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，非均相液体是极其重要的。典型的例子是纳米多孔碳中的电解质溶液，以及细胞内限制中的蛋白质-药物相互作用。人们在不同的简化程度上尝试了在界面和纳米限制下模拟液体，从药物跨生物膜的传输估计为水和辛醇的大块液体相之间的分配，到纳米颗粒跨脂双层传输的粗粒度模拟。 目前，在化学和生物分子体系和纳米材料的纳米尺度约束中，需要能够充分考虑溶剂分子结构的溶剂化理论模型。这种理论模型对扩展分子模拟的能力有很大的需求，分子模拟到目前为止还不足以解决从快到慢的整个尺度上的复杂现象和过程，在感兴趣的大型纳米系统中。 基于统计力学第一原理的液体积分方程论为处理溶液中复杂的化学和生物分子系统提供了坚实的平台。特别是，具有Kovalenko-Hirata闭合关系(3D-RISM-KH分子溶剂化理论)的三维参考相互作用点模型为溶液中的许多体系提供了机理、洞察力和性质预测，否则将服从分子模拟或连续溶剂化处理。3D-RISM-KH已经进入实用阶段，并在多尺度方法中结合了量子化学、MD和DPD模拟方法以及配体对接协议，这些开发在主要软件包中实施：阿姆斯特丹密度泛函(ADF)计算化学软件包、Amber MD软件包、AutoDock对接工具套件和分子操作环境(MoE)药物发现套件。 该项目将在液体界面和受限液体的非均匀3D-RISM-KH分子理论中结合3D-RISM-KH和SS-LMBW方法，并将其应用于复杂的化学和生物分子问题，包括：(I)阿尔茨海默氏症和肌萎缩侧索硬化症治疗的药物发现和跨生物膜以及血脑屏障的传输，(Ii)预测纤维素纳米晶(CNC)纳米颗粒在生物膜上的转移到纳米毒性数据库，以及(Iii)用于储能装置的纳米多孔碳材料中的纳米颗粒。新的方法学发展将被添加到教育部(加拿大)和ADF(荷兰)软件包的现有实施中。两名博士生将参与并接受该项目的培训。

It is widely recognized that solvation is critical for a broad range of science and technology. In particular, inhomogeneous liquid phases are of paramount importance in a variety of technological applications of chemistry, electrochemistry, biocatalysis, biology, and pharmacology. Representative examples are electrolyte solution in nanoporous carbon, and protein-drug interactions in intracellular confinement. Modeling liquids at interfaces and in nano-confinement has been attempted at different levels of simplification, 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 solvation theoretical models that adequately include molecular structure of solvent in nanoscale confinement of chemical and biomolecular systems 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. Based on the first principles of statistical mechanics, integral equation theory of liquids provides a firm platform to handle complex chemical and biomolecular systems in solution. In particular, the three-dimensional reference interaction site model with the Kovalenko-Hirata closure relation (3D-RISM-KH molecular theory of solvation) has provided mechanisms insights and properties predictions for a number of systems in solution otherwise amenable to molecular simulation or continuum solvation treatment. 3D-RISM-KH 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, and Molecular Operating Environment (MOE) drug discovery suite. This project will couple the 3D-RISM-KH and SS-LMBW approaches in an inhomogeneous 3D-RISM-KH molecular theory of liquid interfaces and confined liquids, and will apply it to complex chemical and biomolecular problems, including: (i) drug discovery and transport across biomembranes and the blood-brain barrier for Alzheimer's and ALS therapeutics, (ii) prediction of cellulose nanocrystals (CNC) nanoparticles translocation across biomembranes towards nanotoxicity database, and (iii) nanoparticles in nanoporous carbon material for energy storage devices. The new methodological developments will be added to the existing implementations in the MOE (Canada) and ADF (Netherlands) software packages. Two PhD students will be involved and trained on this project.