Hydrogen/deuterium exchange (HDX) is a powerful technique to investigate protein
conformational dynamics at amino acid resolution. Because HDX provides a measurement
of solvent exposure of backbone hydrogens, ensemble-averaged over potentially slow
kinetic processes, it has been challenging to use HDX protection factors to refine structural
ensembles obtained from molecular dynamics simulations. This entails two dual
challenges:(1) identifying structural observables that best correlate with backbone amide …

680a Wednesday, February 21, 2018 residue i, is characterized by a protection factor, PFi=
kex, i/kint, i, which is related to the effective free energy difference between open and closed
states, DG, through ln (PFi)= bDGi. However, it has been challenging to make direct
connections between molecular simulations of native-state protein dynamics, both in
predicting HDX PF from trajectory data, and in using experimental protection factors as
restraints in simulated ensembles. In this study, we propose an expression, ln (PF)= bc< …