Cell Method to Calculate Solution Free Energies from Computer Simulation

计算机仿真是广泛应用于许多研究领域的有力工具。在这种方法中，感兴趣的系统的模型在计算机上被模拟，以模拟真实系统的行为，而不需要使系统成为现实。模拟可以产生很难甚至不可能通过真实实验获得的信息。原子及其形成的分子之间的相互作用控制着世界的行为。因此，了解它们之间的相互作用可能有助于解释这种行为。分子的纳米尺度使得直接研究它们变得困难，这使得它们成为计算机模拟的主要候选者。其中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的行为，例如水是否会冻结，油和水是否会混合，药物是否会与目标结合等。要应用计算机模拟来研究分子性质，人们需要一个理论来将分子尺度上的相互作用与它们在更大尺度上的行为联系起来。对于大多数感兴趣的体系，目前的方法仍然不能从计算机模拟中计算出足够的自由能。该提议旨在开发一种有可能计算任何分子计算机模拟的自由能的方法。该方法基于一种相当古老的方法，称为细胞理论。细胞理论不是试图一次研究所有的分子，而是在相邻分子的平均环境中分别对待每个分子。细胞理论是在计算机出现之前发展起来的，它不能有效地计算这种平均环境，因此用处不大。然而，由于计算机模拟现在正在做所有计算平均环境的艰苦工作，我已经展示了如何成功地应用晶胞理论来计算作为测试的简单液体的模拟的准确自由能。该提案描述了将这一简单而实用的方法扩展到更复杂系统的模拟。此外，该方法还将用于了解液体的性质以及分子如何在其中溶解。

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.