Salt effects on hydrophobic-core formation in folding of a helical miniprotein studied by molecular dynamics simulations.
We have investigated effects of salt ions on folding events of a helical miniprotein chicken villin headpiece subdomain HP36. Low concentrations of ions alter electrostatic interactions between charged groups of a protein and can change the populations of conformers. Here, we compare two data sets of folding simulations of HP36 in explicit water solvent with or without ions. For efficient sampling of the conformational space of HP36, the multicanonical replica-exchange molecular dynamics method was employed. Our analyses suggest that salt alters salt-bridging nature of the protein at later stages of folding at room temperature. Especially, more nonnative, nonlocal salt bridges are formed at near-native conformations in pure water. Our analyses also show that such salt-bridge formation hinders the fully native hydrophobic-core packing at the final stages of folding.
Nagahama Institute of Bio-Science and Technology, Tamura, Nagahama, Shiga, 526-0829, Japan; RIKEN Advanced Institute for Computational Science, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Takao
T
Yoda
Yuji
Y
Sugita
Yuko
Y
Okamoto
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry*; D002645:Chickens; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011189:Potassium Chloride / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D030161:Avian Proteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C115223:villin headpiece subdomain peptide; D011189:Potassium Chloride
free-energy landscape; multicanonical replica-exchange method; protein folding; salt bridge; salt ion