title: Redox potentials of protein disulfide bonds from free-energy calculations.
abstract: Thiol/disulfide exchange in proteins is a vital process in all organisms. To ensure specificity, the involved thermodynamics and kinetics are believed to be tailored by the structure and dynamics of the protein hosting the thiol/disulfide pair. We here aim at predicting the thermodynamics of thiol/disulfide pairs in proteins. We devise a free-energy calculation scheme, which makes use of the Crooks Gaussian intersection method to estimate the redox potential of thiol/disulfide pairs in 12 proteins belonging to the thioredoxin superfamily, namely, thioredoxins, glutaredoxins, and thiol-disulfide oxidoreductases in disulfide bond formation systems. We obtained a satisfying correlation of computed with experimental redox potentials (varying by 160 mV), with a residual error of ∼40 mV (8 kJ/mol), which drastically reduces when considering a less diverse set of only thioredoxins. Our simple and transferrable approach provides a route toward estimating redox potentials of any disulfide-containing protein given that its (reduced or oxidized) structure is known and thereby represents a step toward a rational design of redox proteins.
authors: †Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.
authors: Wenjin
authors: W
authors: Li
authors: †Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.
authors: Ilona B
authors: IB
authors: Baldus
authors: †Heidelberg Institute for Theoretical Studies, Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany.
authors: Frauke
authors: F
authors: Gräter
mesh_terms: D020816:Amino Acid Motifs; D004220:Disulfides / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D013816:Thermodynamics; D013879:Thioredoxins / Q000737:chemistry*
chemical_list: D004220:Disulfides; D013879:Thioredoxins