TY - JOUR AU - Mohanty, Sandipan AU - Meinke, Jan AU - Zimmermann, Olav TI - Folding of Top7 in unbiased all-atom Monte Carlo simulations JO - Proteins VL - 81 IS - 8 SN - 0887-3585 CY - New York, NY PB - Wiley-Liss M1 - FZJ-2013-01895 SP - 1446 - 1456 PY - 2013 AB - 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. LB - PUB:(DE-HGF)16 UR - <Go to ISI:>//WOS:000329220400014 C6 - pmid:23553942 DO - DOI:10.1002/prot.24295 UR - https://juser.fz-juelich.de/record/133447 ER -