title: Effect of hexafluoroisopropanol alcohol on the structure of melittin: a molecular dynamics simulation study.
abstract: The molecular mechanism by which HFIP stabilizes the alpha-helical structure of peptides is not well understood. In the present study, we use melittin as a model to gain insight into the details of the atomistic interactions of HFIP with the peptide. We have performed extensive comparative molecular dynamics simulations (up to 100 nsec) in the absence and in the presence of HFIP. In agreement with recent NMR experiments, the simulations show rapid loss of tertiary structure in water at pH 2 but much higher helicity in 35% HFIP. The MD simulations also indicate that melittin adopts a highly dynamic global structure in 35% HFIP solution with two alpha-helical segments sampling a wide range of angular orientations. The analysis of the HFIP distribution shows the tendency of HFIP to aggregate around the peptide, increasing the local cosolvent concentration to more than two times that in the bulk concentration. The correlation of local peptide structure with HFIP coating suggests that displacement of water at the peptide surface is the main contribution of HFIP in stabilizing the secondary structure of melittin. Finally, a stabilizing effect promoted by the presence of counter-ions was also observed in the simulations.
authors.affiliation: School of Engineering and Science, International University of Bremen, Campus Ring 1, D-28725 Bremen, Germany. d.roccatano@iu-bremen.de
authors.forename: Danilo
authors.initials: D
authors.lastname: Roccatano
authors.forename: Marco
authors.initials: M
authors.lastname: Fioroni
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
mesh_terms: D003198:Computer Simulation; D008555:Melitten / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D020005:Propanols / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D006845:Hydrocarbons, Fluorinated
chemical_list: D008555:Melitten; D020005:Propanols; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated