Solvation in protein (un)folding of melittin tetramer-monomer transition
Protein structural integrity and flexibility are intimately tied to solvation. Here, we examine the effect that changes in bulk and local solvent properties have on protein structure and stability. We observe the change in solvation of an unfolding of the protein model, melittin, in the presence of a denaturant, trifluoroethanol. The peptide system displays a well defined transition in that the tetramer unfolds without disrupting the secondary or tertiary structure. In the absence of local structural perturbation, we are able to reveal exclusively the role of solvation dynamics in protein structure stabilization and the (un)folding pathway. A sudden retardation in solvent dynamics, which is coupled to the change in protein structure, is observed at a critical trifluoroethanol concentration. The large amplitude conformational changes are regulated by the local solvent hydrophobicity and bulk solvent viscosity.
Additional Information©2009 National Academy of Sciences. Contributed by Ahmed H. Zewail, May 29, 2009 (sent for review May 1, 2009). Published online before print July 21, 2009, doi: 10.1073/pnas.0905967106 We thank Dr. Hans Frauenfelder for his careful reading of the manuscript and his suggestion for the consideration of the stretched exponential function in the fitting of the solvation of the protein. This work was supported by the National Science Foundation and Air Force Office of Scientific Research in the Gordon and Betty Moore Center for Physical Biology at Caltech. Author contributions: C.M.O., O.-H.K., M.M.L., and A.H.Z. designed research, performed research, analyzed data, and wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/cgi/content/full/0905967106/DCSupplemental.
Published - Othon2009p5577P_Natl_Acad_Sci_Usa.pdf
Supplemental Material - 0905967106SI.pdf