title: Defining the nature of thermal intermediate in 3 state folding proteins: apoflavodoxin, a study case.
abstract: The early stages of the thermal unfolding of apoflavodoxin have been determined by using atomistic multi microsecond-scale molecular dynamics (MD) simulations complemented with a variety of experimental techniques. Results strongly suggest that the intermediate is reached very early in the thermal unfolding process and that it has the properties of an "activated" form of the native state, where thermal fluctuations in the loops break loop-loop contacts. The unrestrained loops gain then kinetic energy corrupting short secondary structure elements without corrupting the core of the protein. The MD-derived ensembles agree with experimental observables and draw a picture of the intermediate state inconsistent with a well-defined structure and characteristic of a typical partially disordered protein. Our results allow us to speculate that proteins with a well packed core connected by long loops might behave as partially disordered proteins under native conditions, or alternatively behave as three state folders. Small details in the sequence, easily tunable by evolution, can yield to one or the other type of proteins.
authors.affiliation: Joint IRB BSC Program in Computational Biology, Institute for Research in Biomedicine, Barcelona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: García-Fandiño
authors.forename: Pau
authors.initials: P
authors.lastname: Bernadó
authors.forename: Sara
authors.initials: S
authors.lastname: Ayuso-Tejedor
authors.forename: Javier
authors.initials: J
authors.lastname: Sancho
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D000595:Amino Acid Sequence; D001059:Apoproteins / Q000737:chemistry*; D005418:Flavodoxin / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D001059:Apoproteins; D005418:Flavodoxin; C026932:apoflavodoxin