Expanding the toolkit for membrane protein modeling in Rosetta

Motivation: A range of membrane protein modeling tools has been developed in the past 5-10 years, yet few of these tools are integrated and make use of existing functionality for soluble proteins. To extend existing methods in the Rosetta biomolecular modeling suite for membrane proteins, we recently implemented RosettaMP, a general framework for membrane protein modeling. While RosettaMP facilitates implementation of new methods, addressing real-world biological problems also requires a set of accessory tools that are used to carry out standard modeling tasks. Results: Here, we present six modeling tools, including de novo prediction of single trans-membrane helices, making mutations and refining the structure with different amounts of flexibility, transforming a protein into membrane coordinates and optimizing its embedding, computing a Rosetta energy score, and visualizing the protein in the membrane bilayer. We present these methods with complete protocol captures that allow non-expert modelers to carry out the computations.