Molecular dynamics of ferrocytochrome c

Abstract

The cytochromes c function as single-electron carriers in the mitochondrial electron transport chain^1,2. The native structures of the proteins from different species are quite similar^1,2, as are the structures of the reduced and oxidized forms^3,4. The 103-residue polypeptide chain of tuna cytochrome c contains 5 α-helical segments (residues 2–13, 50–54, 61–69, 71–74, 89–100); the haem group is almost completely buried in a hydrophobic pocket and is covalently bonded to the polypeptide chain by thioether linkages involving Cys 14 and Cys 17 and by linkages to the iron involving His 18 and Met 80 (refs 1–3). NMR^5,6 and hydrogen exchange^7,8 studies indicate significant internal mobility in cytochrome c. In spite of the apparent similarity of the time-average structures of the reduced and oxidized proteins, the structural fluctuations are significantly larger in the latter form^2,7,8. It has been suggested that the internal motions have a role in the electron transfer mechanism^2,9. A 16-ps computer simulation^10–14 of the atomic motions in reduced tuna cytochrome c has now been completed; this reveals various correlations between the magnitudes of the atomic position fluctuations and the structural features of the protein.