Flex ddG: Rosetta Ensemble-Based Estimation of Changes in Protein-Protein Binding Affinity upon Mutation.

ABSTRACT: Computationally modeling changes in binding free energies upon mutation (interface ΔΔ G) allows large-scale prediction and perturbation of protein-protein interactions. Additionally, methods that consider and sample relevant conformational plasticity should be able to achieve higher prediction accuracy over methods that do not. To test this hypothesis, we developed a method within the Rosetta macromolecular modeling suite (flex ddG) that samples conformational diversity using "backrub" to generate an ensemble of models and then applies torsion minimization, side chain repacking, and averaging across this ensemble to estimate interface ΔΔ G values. We tested our method on a curated benchmark set of 1240 mutants, and found the method outperformed existing methods that sampled conformational

SUBMITTER: Barlow KA 

PROVIDER: S-EPMC5980710 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature