Methods of comparison between simulated and experimental HDX.
(a) Protein structures representative of experimental HDX conditions can be leveraged against models generated from conformational sampling techniques. (i) Molecular dynamics simulations or (ii) dihedral space sampling can be used to generate diverse conformational ensembles (iii). (iv,v) Protection factors (typically used as the natural logarithm of the protection factor; lnP) can be simulated from models and averaged across trajectories to provide ensemble-averaged approximations that can be compared with experimental HDX values. (b) Docking methods relying on (i) structural complementarity or guided by experimental restraints can be used to generate libraries of candidate models (ii). (iii,iv) Simulated protection factors for bound vs unbound states can be compared with experimentally calculated values and used to score plausible models.