Protein structure prediction using residue-resolved protection factors from hydrogen-deuterium exchange NMR

Abstract

Hydrogen-deuterium exchange (HDX) measured by nuclear magnetic resonance (NMR) provides structural information for proteins relating to solvent accessibility and flexibility. While this structural information is beneficial, the data cannot be used exclusively to elucidate structures. However, the structural information provided by the HDX-NMR data can be supplemented by computational methods. In previous work, we developed an algorithm in Rosetta to predict structures using qualitative HDX-NMR data (categories of exchange rate). Here we expand on the effort, and utilize quantitative protection factors (PFs) from HDX-NMR for structure prediction. From observed correlations between PFs and solvent accessibility/flexibility measures, we present a scoring function to quantify the agreement with HDX data. Using a benchmark set of 10 proteins, an average improvement of 5.13Å in root-mean-square deviation (RMSD) is observed for cases of inaccurate Rosetta predictions. Ultimately, seven out of 10 predictions are accurate without including HDX data, and nine out of 10 are accurate when using our PF-based HDX score.