Accurate Prediction of Amide Exchange in the Fast Limit Reveals Thrombin Allostery.

ABSTRACT: Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) of proteins has become extremely popular for identifying ligand-binding sites, protein-protein interactions, intrinsic disorder, and allosteric changes upon protein modification. Such phenomena are revealed when amide exchange is measured in the fast limit, that is, within a few minutes of exchange in deuterated buffer. The HDXMS data have a resolution of the length of peptides and are difficult to interpret because many different phenomena lead to changes in hydrogen/deuterium exchange. We present a quantitative analysis of accelerated molecular dynamics simulations that provides impressive agreement with peptide-length HDXMS data. Comparative analysis of thrombin and a single-point mutant reveals that the simulation analysis can

SUBMITTER: Markwick PRL 

PROVIDER: S-EPMC6342732 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature