Calculation of organic solvent–water partition coefficients of iron–sulfur protein models

Abstract

A method is presented that permits semiquantitative estimation of the partitioning of many solutes between many pairs of media. As an example, the organic solvent–water partition coefficients P are calculated. The only needed parameters are the dielectric constant and molecular volume of the organic solvent. Fe 4S 4Cys n models of high-potential FeS proteins are studied. The Gibbs free energies of solvation and partition coefficients for Fe 4S 4Cys n are calculated. The organic solvent–water partition coefficients for 1-octanol P o, cyclohexane P ch and chloroform P cf decrease 4.41, 6.22 and 4.60 log units per cysteine (Cys) ligand, respectively. P o results are compared with CDHI calculations and P ch and P cf results are compared with calculations carried out with a method by Leo et al. With these reference methods, P o, P ch and P cf decrease 4.12, 4.70 and 5.63 log units per Cys ligand, respectively. log P o, log P ch and log P cf mean relative errors (MRE) are 17, 26 and −16%, respectively. These represent a MRE of 9% but a mean unsigned relative error (URE) of 19%. For Fe 4S 4, P o, P ch and P cf are close to 0 log unit. On varying the number of Cys units, the structures show hydrophobic moments indicative of particularly amphipathic structures as Fe 4S 4Cys.