In this section
@article{Grimaldi:2026:10.1021/acsphyschemau.5c00127,
author = {Grimaldi, A and Hobbs, B and Stofella, M and Karamanos, TK and Paci, E},
doi = {10.1021/acsphyschemau.5c00127},
journal = {ACS Phys Chem Au},
pages = {446--450},
title = {Amide Hydrogen-Deuterium Exchange in Isotopically Mixed Water.},
url = {http://dx.doi.org/10.1021/acsphyschemau.5c00127},
volume = {6},
year = {2026}
}
TY - JOUR
AB - Hydrogen-deuterium exchange (HDX) of protein backbone amides provides a powerful probe of conformational dynamics. However, when experiments are performed in H2O/D2O mixtures, quantitative interpretation is hindered by back exchange and isotope effects not captured by the classical Linderstrom-Lang (LL) model. We introduce a generalized Linderstrom-Lang (GLL) framework that explicitly accounts for forward and reverse exchange and for changes in protection upon isotopic substitution. Analytical solutions describe equilibrium enrichment (fractionation) and protection factors in mixtures, reducing to the LL model in pure D2O. Application to HDX/NMR of the molecular chaperone DNAJB1 in 50% D2O demonstrates that the GLL model recovers protection factors at 100% D2O. Ignoring back exchange (i.e., using the LL model), protection factors are systematically underestimated. A particularly powerful feature of our approach is that a single HDX experiment in a mixture (e.g., 50% D2O) simultaneously provides protection factors that report on conformational dynamics and local stability and fractionation factors that are sensitive to the local hydrogen-bonding environment.
AU - Grimaldi,A
AU - Hobbs,B
AU - Stofella,M
AU - Karamanos,TK
AU - Paci,E
DO - 10.1021/acsphyschemau.5c00127
EP - 450
PY - 2026///
SP - 446
TI - Amide Hydrogen-Deuterium Exchange in Isotopically Mixed Water.
T2 - ACS Phys Chem Au
UR - http://dx.doi.org/10.1021/acsphyschemau.5c00127
UR - https://www.ncbi.nlm.nih.gov/pubmed/42221934
VL - 6
ER -
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