The Non-Covalent Chemistry of Complex Systems

非共价相互作用的精确定量描述将提供解开凝聚相分子性质的复杂性的关键。虽然我们开始能够预测的三维结构与一些信心，预测的热力学决定的功能性质仍然远远超出了我们目前的能力。在21世纪的世纪，我们渴望分子工程的学科，但这种描述是一个很长的路要走的现实是什么实际发生在任何实验室，试图产生一个功能分子。该提案的目的是开发一系列新的工具，这些工具将允许基于分子间力的新超分子视角将分子特性精确映射到化学结构上。我们选择作为我们的参考框架的分子表面上的特定识别位点之间的单个点接触。这些是我们可以在实验系统中轻松识别和量化的相互作用类型。这将使我们能够建立分子参数之间的连接，可以从第一原理计算与超分子模型系统的实验行为和分子系综的散装性能。我们相信，这种方法有可能为非共价化学如何决定复杂系统的功能特性提供全新的见解，并跨越分子科学的所有学科。这些方法将在一系列代表当前实际和科学挑战的分子设计问题中进行测试，例如预测蛋白质-配体亲和力、相分配、溶解度、共晶形成、表面粘附、摩擦和反应性的非共价控制。其目标是产生一种预测和理解任何分子系统的热力学性质的通用方法。这种新的超分子表面接触方法有望完全改变我们对溶液，界面和固体中分子相互作用的看法，这种方式可以被分子科学中的每个人所采用。

An accurate quantitative description of non-covalent interactions will provide the key to unravelling the complexity of condensed phase molecular properties. Although we are beginning to be able to predict three-dimensional structure with some confidence, prediction of the thermodynamics that dictate functional properties remains well beyond our reach at present. In the 21st century, we aspire to the discipline of molecular engineering, but this description is a long way from the reality of what actually takes place in any laboratory that attempts to produce a functional molecule. The aim of this proposal is to develop a range of new tools that will allow the accurate mapping of molecular properties onto chemical structure, based on a new supramolecular perspective on intermolecular forces. We choose as our frame of reference individual point contacts between specific recognition sites on molecular surfaces. These are the types of interactions that we can easily identify and quantify in experimental systems. This will allow us to build a connection between molecular parameters that can be calculated from first principles with the experimental behaviour of supramolecular model systems and the bulk properties of molecular ensembles. We believe that this approach has the potential to deliver radically new insights into how non-covalent chemistry determines the functional properties of complex systems and cuts across all disciplines in the molecular sciences. The methods will be tested in a range of molecular design problems that represent current practical and scientific challenges, such as prediction of protein-ligand affinity, phase partitioning, solubility, cocrystal formation, surface adhesion, friction and non-covalent control of reactivity. The goal is to produce a general method for predicting and understanding the thermodynamic properties of any molecular system. This new supramolecular surface contact approach promises to completely change the way we think about the molecular interactions in solutions, interfaces and solids in a way that can be adopted by everyone involved in the molecular sciences.