Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

52-POS Board 12 Fast High-Resolution Refinement of Large Proteins and Membrane Protein Complexes in Rosetta Julia Koehler Leman 1,2 , Jeffrey J. Gray 3 , Richard Bonneau 1,2 . 1 Simons Foundation, New York, NY, USA, 2 New York University, New York, NY, USA, 3 Johns Hopkins University, Baltimore, MD, USA. Protein structure refinement is one of the most often used modeling applications, especially for high-resolution refinement of structures from homology modeling, de novo structure prediction, loop modeling; to create starting models for protein design, protein-protein docking or ligand docking; to refine structures into density maps from crystallography and cryoEM; to create all- atom representations from coarse-grained models; and to model protein conformational flexibility. Here, we present a new high-resolution refinement algorithm implemented into the Rosetta software suite. Since Rosetta was historically developed for small, soluble proteins, the gold-standard refinement algorithm in Rosetta, FastRelax, was neither routinely used, nor benchmarked on large to very large, asymmetric proteins. When applied to larger complexes, such as membrane proteins, FastRelax becomes prohibitively expensive. We show that our new RangeRelax algorithm does not only speed up refinement of complexes up to ~5000 residues by up to 60-fold, but it also results in fewer clashes and better stereochemistry. RangeRelax is available for soluble and for membrane proteins and can be easily integrated into larger modeling protocols.

87