Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction.

By Colin A. Smith, Tanja Kortemme. 2008

317 citations recorded by the source corpus.

Subfields: Materials Chemistry, Molecular Biology

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Citations in the corpus

Multi-state design of flexible proteins predicts sequences optimal for conformational change (2019, methodology): “The structural ensembles used for this approach were generated by reverting all structural side chains to a consensus sequence and employing ROSETTA Backrub to introduce small local rotation about the Cα-Cα axis of each of three-residue segments while maintaining ideal bond length, angle, and the st”
Methods in Enzymology: “Flexible backbone sampling methods to model and design protein alternative conformations” (2013, unknown): “Similarly, the ability of backrub to sample functionally important loop conformations has been demonstrated for triosephosphate isomerase (TIM; Smith & Kortemme, 2008).”
Flex ddG: Rosetta Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity Upon Mutation (2017, background): “30 The backrub method samples local side chain and backbone conformational changes, similar to those suggested to underlie observed conformational heterogeneity in high-resolution crystal structures, 31 and to accommodate evolved and designed mutations.”
Protein engineering by highly parallel screening of computationally designed variants (2016, methodology): “For this strategy, alternative protein backbones and amino acids are explored within the same sampling scheme, whereby alternative protein backbones are created by rotating atoms around an axis defined by two Ca atoms and alternative amino acid side chains are sampled using the Dunbrack rotamer libr”
A smoothed backbone-dependent rotamer library for proteins derived from adaptive kernel density estimates and regressions (2011, unknown): “Backbone flexibility is increasingly incorporated into comparative modeling and protein design (Friedland et al., 2008; Smith and Kortemme, 2008).”
MODELING AND INFERENCE OF SEQUENCE-STRUCTURE SPECIFICITY (2009, methodology): “Decoy backbones were generated using ROSETTA’s backrub generating mode, which generates backbones by manipulating the backbone dihedrals and pruning away energetically unfavorable conformations [21, 5].”
A Web Resource for Standardized Benchmark Datasets, Metrics, and Rosetta Protocols for Macromolecular Modeling and Design (2015, methodology): “Rosetta protocol: There are two main computational steps: (i) the Rosetta Backrub application [35] uses Monte Carlo sampling starting from a single input structure to create an ensemble of near-native conformations; (ii) the sequence tolerance application [39,40] then uses a genetic algorithm to sam”
Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity (2015, methodology): “However, changes in the protein backbones to accommodate changes in amino acid sequence [25] are the rule rather than the exception, and a key reason for failed designs is that they do not adopt the required precise geometry of an engineered functional site [6,18].”
Protein sequence design with a learned potential (2020, methodology): “One failure mode of Rosetta-FixBB is its convergence to highly similar sequences, a deficiency that is handled somewhat but not entirely by protocols that interleave backbone relaxes during design, such as our baseline Rosetta-RelaxBB protocol and Backrub [51, 52, 53].”
Flexible backbone assembly and refinement of symmetrical homomeric complexes (2018, methodology): “Relax, Backrub, and normal mode analysis (NMA) with perturbation steps of 1 Å were each used to produce 50 structures, resulting in an ensemble of 150 structures per target.”
Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences (2015, methodology): “The backrub motion involves rotation of a rigid backbone around axes between nearby Cα atoms, and has been shown to recapitulate alternative backbone conformations in high-resolution crystal structures [30] as well as improving prediction of the conformation of point mutant side chains [31].”
Role of conformational sampling in computing mutation-induced changes in protein structure and stability (2010, background): “12,13 Our goal was to generate ensembles with levels of structural perturbation similar to those generated with back rub while restricting bond lengths and angles to ideal values (see Supporting Information), since the addition of bond length and bond angle degrees of freedom and associated…”
Efficient Flexible Backbone Protein-Protein Docking for Challenging Targets (2017, methodology): “…perturbation of the backbones along the normal modes by 1A˚ et al. , 2001) [using RosettaScripts (Fleishman et al. , 2011)], refinement using the Relax protocol in Rosetta (Tyka et al. , 2011), and backbone flexing using the Rosetta Backrub protocol (Smith and Kortemme, 2008). et al. , 2003b).”