Cell Method to Calculate Solution Free Energies from Computer Simulation

计算机仿真是一种强有力的工具，广泛应用于许多研究领域。在这种方法中，在计算机上模拟感兴趣的系统的模型，以模仿真实的系统的行为，而不需要使系统在现实中。模拟可以产生真实的实验难以甚至不可能获得的信息。原子和它们形成的分子之间的相互作用控制着世界的行为。因此，了解它们的相互作用可能有助于解释这种行为。分子的纳米尺度使它们很难直接研究，这使它们成为计算机模拟的主要候选者。一个重要的量是自由能。自由能描述了系统的稳定性，并使人们能够预测系统将如何表现，例如，将水冻结，将油和水混合，将药物结合到目标等，以应用计算机模拟来研究分子特性，人们需要一个理论来将分子尺度上的相互作用与更大尺度上的行为联系起来。目前的方法仍然不能充分计算的自由能从计算机模拟的大多数系统的兴趣。本建议的目的是开发一种方法的潜力，计算自由能的任何分子计算机模拟。该方法基于一种相当古老的方法，称为细胞理论。细胞理论不是试图同时观察所有分子，而是将每个分子单独放在其相邻分子的平均环境中。在计算机出现之前，细胞理论就已经发展起来，无法有效地计算这种平均环境，使其几乎没有用处。然而，随着计算机模拟现在做所有的艰苦工作，计算这个平均环境，我已经展示了如何细胞理论可以成功地应用于计算准确的自由能从一个简单的液体模拟作为一个测试。该提案描述了这种直接和实用的方法来模拟更复杂的系统的扩展。此外，该方法将用于了解液体的性质以及分子如何溶解在其中。

Computer simulation is a powerful tool widely used in many fields of research. In this approach, a model of the system of interest is simulated on a computer to mimic how the real system behaves without the need to make the system in reality. Simulation can produce information that is difficult or even impossible to obtain by real experiment.The interactions of atoms and of the molecules they form control how the world behaves. Therefore, an understanding of their interactions may help explain such behaviour. The nanoscale of molecules makes them difficult to study directly, and this renders them a prime candidate for computer simulation.One important quantity is the free energy. The free energy describes a system's stability and enables one to predict how the system will behave e.g. will water freeze, will oil and water mix, will a drug bind to a target etc. To apply computer simulation to investigate molecular properties, one needs a theory to relate the interactions on the molecular scale to their behaviour on the larger scale. Current methods are still incapable of calculating adequately the free energy from a computer simulation for most systems of interest.This proposal aims to develop a method with the potential to calculate the free energy for any molecular computer simulation. The method is based on a rather venerable approach called cell theory. Instead of trying to look at all molecules at once, cell theory treats each molecule separately in the average environment of its neighbours. Developed before the advent of computers, cell theory had been incapable of effectively calculating this average environment, rendering it of little use. However, with a computer simulation now doing all the hard work of calculating this average environment, I have shown how cell theory can be successfully applied to calculate accurate free energies from a simulation of a simple liquid as a test. The proposal describes the extension of this straightforward and practical approach to simulations of more complex systems. In addition, the method will be used to understand the properties of liquids and how molecules dissolve in them.