Multiscale modeling of liquid interfacial phases in biomolecular environments and nanomaterials

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，非均匀液相在化学、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。 代表性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。在不同的简化水平上尝试了在界面处和纳米限制中对液体进行建模，从估计为水和辛醇的本体液相之间的分配的药物跨生物膜的运输，到跨脂质双层的纳米颗粒移位的粗粒度模拟。目前，有必要的溶剂化理论模型，充分包括在化学和生物分子系统和纳米材料的纳米尺度限制溶剂的分子结构。这种理论模型对于扩展分子模拟的能力具有很大的需求，分子模拟的能力目前还不足以解决感兴趣的大型纳米系统中从快到非常慢的整个尺度范围内的复杂现象和过程。基于统计力学的第一原理，液体积分方程理论为处理溶液中复杂的化学和生物分子体系提供了坚实的平台。特别是，三维参考相互作用网站模型与Kovalenko-Hirata封闭关系（3D-RISM-KH分子溶剂化理论）提供了机制的见解和性质预测的一些系统在解决方案，否则服从分子模拟或连续溶剂化处理。3D-RISM-KH已经发展到实用性的状态，并与量子化学、MD和DPD模拟方法以及配体对接协议在多尺度方法中耦合-主要软件包中实施的开发：Amsterdam密度泛函（ADF）计算化学包、Amber MD包、AutoDock对接工具套件和分子操作环境（莫伊）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分子理论中耦合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）用于阿尔茨海默病和ALS治疗的药物发现和跨生物膜和血脑屏障的运输，（ii）预测纤维素纳米晶体（CNC）纳米颗粒跨生物膜向纳米毒性数据库的易位，以及（iii）用于能量存储装置的纳米多孔碳材料中的纳米颗粒。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。两名博士生将参与该项目并接受培训。*

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.********