Some methods for binding prediction require extensive knowledge and expertise. For example, a person with little computational experience may not be able to conduct a successful free energy calculation given the historical difficulty of setting up such simulations. Few available software tools are user-friendly enough that one might be able to simply insert receptor and ligand files and obtain an accurate estimate of a property like a binding free energy. This likely affects accuracy; it's conceivable that users providing the same input files to the same package could obtain dramatically different results because of different choices of protocol. Some tools provide a relatively straightforward interface for free energy calculations, at least, like YANK, but even YANK still requires a command-line interface and a wide variety of settings can affect computed values. Other tools like those from Schrödinger and the Chemical Computing Group allow free energy calculations from a GUI (Graphical User Interface), and the Schrödinger tools remove many key choices from the hands of users. However, we are not yet aware of a successful application of these tools to host-guest binding.