title: Protein unfolding pathways explored through molecular dynamics simulations.
abstract: Herein we describe the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in solution at a variety of temperatures both with and without disulfide bonds. The reduced form of the protein unfolded at high temperature to an ensemble of conformations with all the properties of the molten globule state. In this account we outline the structural details of the actual unfolding process between the native and molten globule states. The first steps of unfolding involved expansion of the protein, which disrupted packing interactions. The solvent-accessible surface area also quickly increased. The unfolding was localized mostly to the turn and loop regions of the molecule, while leaving the secondary structure intact. Then, there was more gradual unfolding of the secondary structure and non-native turns became prevalent. This same trajectory was continued and more drastic unfolding occurred that resulted in a relatively compact state devoid of stable secondary structure.
authors.affiliation: Beckman Laboratories for Structural Biology, Stanford University School of Medicine, CA 94305-5400.
authors.forename: V
authors.initials: V
authors.lastname: Daggett
authors.forename: M
authors.initials: M
authors.lastname: Levitt
mesh_terms: D007611:Aprotinin / Q000737:chemistry*; D003198:Computer Simulation; D004220:Disulfides / Q000737:chemistry; D006358:Hot Temperature; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012996:Solutions
chemical_list: D004220:Disulfides; D012996:Solutions; D007611:Aprotinin