Using Rosetta for RNA homology modeling.

Abstract

The three-dimensional structures of RNA molecules provide rich and often critical information for understanding their functions, including how they recognize small molecule and protein partners. Computational modeling of RNA 3D structure is becoming increasingly accurate, particularly with the availability of growing numbers of template structures already solved experimentally and the development of sequence alignment and 3D modeling tools to take advantage of this database. For several recent "RNA puzzle" blind modeling challenges, we have successfully identified useful template structures and achieved accurate structure predictions through homology modeling tools developed in the Rosetta software suite. We describe our semi-automated methodology here and walk through two illustrative examples: an adenine riboswitch aptamer, modeled from a template guanine riboswitch structure, and a SAM I/IV riboswitch aptamer, modeled from a template SAM I riboswitch structure.