Prediction and Validation of a Protein's Free Energy Surface Using Hydrogen Exchange and (Importantly) Its Denaturant Dependence.

ABSTRACT: The denaturant dependence of hydrogen-deuterium exchange (HDX) is a powerful measurement to identify the breaking of individual H-bonds and map the free energy surface (FES) of a protein including the very rare states. Molecular dynamics (MD) can identify each partial unfolding event with atomic-level resolution. Hence, their combination provides a great opportunity to test the accuracy of simulations and to verify the interpretation of HDX data. For this comparison, we use Upside, our new and extremely fast MD package that is capable of folding proteins with an accuracy comparable to that of all-atom methods. The FESs of two naturally occurring and two designed proteins are so generated and compared to our NMR/HDX data. We find that Upside's accuracy is considerably improved

SUBMITTER: Peng X 

PROVIDER: S-EPMC8757463 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature