The Rosetta all-atom energy function for macromolecular modeling and design

Abstract

Over the past decade, the Rosetta biomolecular modeling suite has informed diverse biological questions and engineering challenges ranging from interpretation of low-resolution structural data to design of nanomaterials, protein therapeutics, and vaccines. Central to Rosetta's success is the energy function: a model parameterized from small molecule and X-ray crystal structure data used to approximate the energy associated with each biomolecule conformation. This paper describes the mathematical models and physical concepts that underlie the latest Rosetta energy function, beta_nov15. Applying these concepts, we explain how to use Rosetta energies to identify and analyze the features of biomolecular models. Finally, we discuss the latest advances in the energy function that extend capabilities from soluble proteins to also include membrane proteins, peptides containing non-canonical amino acids, carbohydrates, nucleic acids, and other macromolecules.

The Sulfur-Linked Analogue of O-GlcNAc (S-GlcNAc) Is an Enzymatically Stable and Reasonable Structural Surrogate for O-GlcNAc at the Peptide and Protein Levels

“…Importantly, we used the newest version of the Rosetta score function that has been used to model and design glycopeptides. 39,40 Substitution of O-GlcNAc with S-GlcNAc in additional synthetic peptides and proteins may present divergent structural features. For example, the linkages will have different bond lengths and may occupy different conformational space due to changes in the exoanomeric effect.…”

Sensitivity to the two peptide bacteriocin plantaricin EF is dependent on CorC, a membrane‐bound, magnesium/cobalt efflux protein

“…Co‐evolutionary constraints were determined using the GREMLIN server (http://gremlin.bakerlab.org/) (Kamisetty, Ovchinnikov, & Baker, ). A 3D structure model of the CorC protein from LP965 was performed using relax application (Conway, Tyka, DiMaio, Konerding, & Baker, ; Khatib et al, ; Nivón, Moretti, & Baker, ; Tyka et al, ) in Rosetta structural modeling software (Alford et al, ; Bender et al, ; Rohl, Strauss, Misura, & Baker, ) and the x‐ray structure of a CorC‐like protein from of Oenococcus oeni PSU (PDB ID: 3OCO) as a template. Sequences were aligned with MUSCLE (Edgar, ) and % identity between the CorC protein sequence and 3OCO was 41% (Figure A4).…”

Distinct structural mechanisms determine substrate affinity and kinase activity of protein kinase Cα

“…The Rosetta software suite has many functionalities that have been shown to perform well consistently, for protein structure refinement and side chain repacking 4 . We have previously combined the GneimoSim software 5 with the Rosetta software to (1) perform torsion MD simulations with Rosetta forcefield 6 and to (2) enhance the conformational sampling during protein structure refinement by combining the benefits torsional MD in GNEIMO with the torsional Monte Carlo sampling and side chain repacking in Rosetta using a rotamer library. The details of the software integration can be found in reference number 5.…”