Protein structure modeling with Rosetta: Case studies in structure prediction and enzyme repurposing

Abstract

The Rosetta protein structure methodology has evolved as a comprehensive tool for protein structure prediction and protein design. The software suite includes modules for protein structure prediction, protein-protein and protein-small molecule docking, as well as protein interface, enzyme, and symmetric protein design. This paper describes two recent Rosetta successes. We describe how Rosetta's structure prediction - when augmented with experimental data - was used to solve difficult molecular replacement problems, yielding high-resolution models for 8 of 13 structures unsolvable by alternate approaches. We also show how Rosetta may be used to redesign metalloenzyme active sites, repurposing a metal binding site to provide new catalytic activity. © 2013 Springer Science+Business Media Dordrecht.