Quantifying protein–ligand binding has attracted the attention of both theorists and experimentalists for decades. Many methods for estimating binding free energies in silico have been reported in recent years. Proper use of the proposed strategies requires, however, adequate knowledge of the protein–ligand complex, the mathematical background for deriving the underlying theory, and time for setting up the simulations, bookkeeping, and postprocessing. Here, to minimize human intervention, we propose a toolkit aimed at facilitating the accurate estimation of standard binding free energies using a geometrical route, coined the binding free-energy estimator (BFEE), and introduced it as a plug-in of the popular visualization program VMD. Benefitting from recent developments in new collective variables, BFEE can be used to generate the simulation input files, based solely on the structure of the complex. Once the simulations are completed, BFEE can also be utilized to perform the post-treatment of the free-energy calculations, allowing the absolute binding free energy to be estimated directly from the one-dimensional potentials of mean force in simulation outputs. The minimal amount of human intervention required during the whole process combined with the ergonomic graphical interface makes BFEE a very effective and practical tool for the end-user.

中文翻译：

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BFEE：易于使用的图形界面，可促进绝对结合自由能计算

数十年来，量化蛋白质与配体的结合引起了理论家和实验家的关注。估算硅中结合自由能的许多方法近年来已有报道。但是，正确使用所提出的策略需要对蛋白质-配体复合物有足够的了解，需要掌握基础理论的数学背景，以及建立模拟，簿记和后处理的时间。在这里，为了最大程度地减少人为干预，我们提出了一个工具包，该工具包旨在促进使用几何路径准确估算标准结合自由能，并创造了结合自由能估计量（BFEE），并将其作为流行的可视化的插件进行了介绍。程序VMD。得益于新的集体变量的最新发展，BFEE可以仅基于复杂系统的结构而用于生成模拟输入文件。模拟完成后，BFEE还可以用于执行自由能计算的后处理，从而可以直接从模拟输出中平均力的一维电位估算绝对结合自由能。在整个过程中所需的最少的人工干预与符合人体工程学的图形界面相结合，使BFEE对于最终用户而言是一种非常有效且实用的工具。