Methodology for rigorous modeling of protein conformational changes by Rosetta using DEER distance restraints.

ABSTRACT: We describe an approach for integrating distance restraints from Double Electron-Electron Resonance (DEER) spectroscopy into Rosetta with the purpose of modeling alternative protein conformations from an initial experimental structure. Fundamental to this approach is a multilateration algorithm that harnesses sets of interconnected spin label pairs to identify optimal rotamer ensembles at each residue that fit the DEER decay in the time domain. Benchmarked relative to data analysis packages, the algorithm yields comparable distance distributions with the advantage that fitting the DEER decay and rotamer ensemble optimization are coupled. We demonstrate this approach by modeling the protonation-dependent transition of the multidrug transporter PfMATE to an inward facing conformation with a

SUBMITTER: Del Alamo D 

PROVIDER: S-EPMC8238229 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature