There are several ways to use Rosetta based on your specific needs. Learn more about each method:
The Command Line Interface is Rosetta's original form, and still the most common way to use Rosetta. Due to the complexity and expense of macromolecular modeling, Rosetta is most often run via a simple command-line interface on distributed-cluster supercomputers. Rosetta offers many different executables, each for addressing a different macromolecular modeling problem. Our documentation explains how to compile and run Rosetta in environments like these, and most demos are built using the command-line tools.
We provide a set of Python bindings that provides the ability to access, modify, and extend Rosetta C++ objects using the Python programming language. PyRosetta is ideal for creating new protocols by combining existing routines or writing new Movers and score terms. PyRosetta is excellent for teaching introductory material to the field, and for rapid prototyping of new ideas and protocols. Go to PyRosetta website.
The PyRosetta Toolkit is a a Graphical User Interface for the Rosetta Software Suite built on PyRosetta, for setting up Rosetta filetypes, analyzing results, running protocols, and doing many other molecular modeling and design tasks. It is distributed with PyRosetta. The code is written in Python, using the Tkinter API, which is distributed with Python itself. As such, it is easy to add new menus, windows, and functions to help in your own modeling and design. The PyRosetta Toolkit is developed by Jared Adolf-Bryfogle from the Dunbrack lab. Read the article in PLOS ONE.
RosettaScripts is an XML script interface that allows users to mix and match Rosetta protocols to customize powerful protocols to their exact needs. RosettaScripts does not have quite the coverage of PyRosetta, but comes as part of the standard C++ build of Rosetta. Therefore, it is straightforward to use RosettaScripts on large supercomputers and distributed computing environments such as BOINC. Indeed, much internal use of Rosetta is via RosettaScripts, and some protocols exist only as their collected objects and an XML script instead of as a standalone executable.
Rosetta does not have a classical graphical user interface. However, many of our developers have simplified the process of using Rosetta somewhat more interactively. For instance, the FoldIt software, which runs atop Rosetta, has a non-game "professional mode" which allows direct, freeform manipulation of protein structures with live scoring and access to simple protocols like rotamer packing and minimization.
The RosettaCommons offers many web-interface servers for the use of Rosetta, which usually allow small academic jobs for free (ROSIE, other servers), or paid use for large or commerical projects Rosetta@cloud. This is the simplest way to try out Rosetta for your problem!