MODELING CHARGE INTERACTIONS AND REDOX PROPERTIES IN DSBA

Accurate prediction of charge interactions in macromolecules presents a significant challenge for computational biology, A model for the low Cys(30) pK(a), and oxidizing power of DsbA (Gane, P.J., Freedman, R. B., and Warwicker, J. (1995) J. Mol. Biol. 249, 376-387) has been inve stigated experimentally (Hennecke, J., Spleiss, C., and Glockshuber, R . (1997) J. Biol. Chem. 272, 189-195), with substitutions for Glu(37) and Glu(38) and with residues 38-40 removed, Measured changes in Cys(3 0) pK(a) and redox potential were relatively small and reported to be in contrast to model predictions, It is now shown, particularly with c alculations of wild-type:mutant differences for a range of salt concen trations, that the data are consistent with the model and support the key finding that a number of different factors contribute to the oxidi zing power of DsbA, so that any particular one need not necessarily be large, A feature of the model is a low protein dielectric, and higher values (which are becoming popular in predictions of pH dependence) a re inconsistent with both the difference data and the wild-type Cys(30 ) pK(a).