Normal mode paths for hydrogen exchange in the peptide ferrichrome.

Possible paths for exposure to solvent and hydrogen exchange of the amide protons of ferrichrome, a cyclic hexapeptide, are examined. The paths are obtained from calculations of the vibrational normal modes of ferrichrome and correspond to low energy atomic displacements away from the local minimum in the multidimensional conformational space of the molecule. Exposure of exchangeable groups along the normal modes was determined by using the solvent accessible surface area algorithm of Lee and Richards. Three of the exchangeable protons (Gly(1,2,3,)) are largely exposed to solvent in the x-ray structure while the remaining three exchangeable protons of the ornithines are totally shielded from solvent. A very small number of normal mode displacements are found to expose the Orn(2) and Orn(3) amide groups while the Orn(1) amide proton remains shielded from solvent for all the paths studied. The effective paths for exposure of Orn(2) and Orn(3) correspond to the lowest frequency ( approximately 18 cm(-1)) motions. The paths are characterized in terms of the magnitude and energy of atomic displacements, correlated changes in dihedral angles, and the resulting changes in exposure and hydrogen bonding of exchangeable groups.