PH-Dependent Protonation of the Phl p 6 Pollen Allergen Studied by NMR and cpH-aMD.

ABSTRACT: We use state-of-the-art NMR experiments to measure apparent pK_a values in the native protein environment and employ a cutting-edge combination of enhanced sampling and constant pH molecular dynamics (MD) simulations to rationalize strong pK_a shifts. The major timothy grass pollen allergen Phl p 6 serves as an ideal model system for both methods due to its high number of titratable residues despite its comparably small size. We present a proton transition analysis as intuitive tool to depict the captured protonation state ensemble in atomistic detail. Combining microscopic structural details from MD simulations and macroscopic ensemble averages from NMR shifts leads to a comprehensive view on pH dependencies of protonation states and tautomers. Overall, w

SUBMITTER: Hofer F 

PROVIDER: S-EPMC6994067 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature