title: Folding of Top7 in unbiased all-atom Monte Carlo simulations.
abstract: For computational studies of protein folding, proteins with both helical and β-sheet secondary structure elements are very challenging, as they expose subtle biases of the physical models. Here, we present reproducible folding of a 92 residue α/β protein (residues 3-94 of Top7, PDB ID: 1QYS) in computer simulations starting from random initial conformations using a transferable physical model which has been previously shown to describe the folding and thermodynamic properties of about 20 other smaller proteins of different folds. Top7 is a de novo designed protein with two α-helices and a five stranded β-sheet. Experimentally, it is known to be unusually stable for its size, and its folding transition distinctly deviates from the two-state behavior commonly seen in natural single domain proteins. In our all-atom implicit solvent parallel tempering Monte Carlo simulations, Top7 shows a rapid transition to a group of states with high native-like secondary structure, and a much slower subsequent transition to the native state with a root mean square deviation of about 3.5 Å from the experimentally determined structure. Consistent with experiments, we find Top7 to be thermally extremely stable, although the simulations also find a large number of very stable non-native states with high native-like secondary structure.
authors.affiliation: Jülich Supercomputing Centre, Institute for Advanced Simulation, Forschungszentrum Jülich, Jülich, Germany. s.mohanty@fz-juelich.de
authors.forename: Sandipan
authors.initials: S
authors.lastname: Mohanty
authors.forename: Jan H
authors.initials: JH
authors.lastname: Meinke
authors.forename: Olav
authors.initials: O
authors.lastname: Zimmermann
mesh_terms: D009010:Monte Carlo Method; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011506:Proteins
keywords: Monte Carlo; Top7; protein folding