Folding of Top7 in unbiased all-atom Monte Carlo simulations

Mohanty, Sandipan; Meinke, Jan; Zimmermann, Olav

doi:10.1002/prot.24295

Journal Article

FZJ-2013-01895

Folding of Top7 in unbiased all-atom Monte Carlo simulations

Mohanty, S. (Corresponding author)FZJ* ; Meinke, J.FZJ* ; Zimmermann, O.FZJ*

2013
Wiley-Liss New York, NY

Proteins 81(8), 1446 - 1456 (2013) [10.1002/prot.24295]

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Please use a persistent id in citations: doi:10.1002/prot.24295

Abstract: For computational studies of protein folding, proteins with both helical and β-sheet secondary structure elements are very challenging, since 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 5 stranded β-sheet. Experimentally it is known to be unusually stable for its size, and its folding transition distinctly deviates from the two state behaviour 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.

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