Heteropolymer modelling and design incorporating quantum chemistry with RosettaQM*

Many current methods for designing, docking, and predicting structures of proteins and other biological heteropolymers rely on force fields. While these permit rapid evaluation of conformational energies and large-scale sampling of conformational and sequence landscapes, force fields offer limited accuracy and generality. Quantum chemistry calculations offer far greater accuracy and generality, but these have long been considered to be intractable in most situations. Nevertheless, recent advancements in approximate and fragment-based methods have brought protein-scale quantum chemistry calculations into the realm of computational tractability. We have worked to build a communications bridge between the Rosetta software suite, widely used for biomolecular modelling, and quantum chemistry software such as GAMESS and Orca, allowing quantum chemistry-based energy calculations in the context of any Rosetta protocol. This presentation will explore the many applications of quantum chemistry calculations for heteropolymer design, docking, and structure prediction.