TY - JOUR
T1 - The dominant interaction between peptide and urea is electrostatic in nature
T2 - A molecular dynamics simulation study
AU - Tobi, Dror
AU - Elber, Ron
AU - Thirumalai, Devarajan
PY - 2003/3
Y1 - 2003/3
N2 - The conformational equilibrium of a blocked valine peptide in water and aqueous urea solution is studied using molecular dynamics simulations. Pair correlation functions indicate enhanced concentration of urea near the peptide. Stronger hydrogen bonding of urea-peptide compared to water-peptide is observed with preference for helical conformation. The potential of mean force, computed using umbrella sampling, shows only small differences between urea and water solvation that are difficult to quantify. The changes in solvent structure around the peptide are explained by favorable electrostatic interactions (hydrogen bonds) of urea with the peptide backbone. There is no evidence for significant changes in hydrophobic interactions in the two conformations of the peptide in urea solution. Our simulations suggest that urea denatures proteins by preferentially forming hydrogen bonds to the peptide backbone, reducing the barrier for exposing protein residues to the solvent, and reaching the unfolded state.
AB - The conformational equilibrium of a blocked valine peptide in water and aqueous urea solution is studied using molecular dynamics simulations. Pair correlation functions indicate enhanced concentration of urea near the peptide. Stronger hydrogen bonding of urea-peptide compared to water-peptide is observed with preference for helical conformation. The potential of mean force, computed using umbrella sampling, shows only small differences between urea and water solvation that are difficult to quantify. The changes in solvent structure around the peptide are explained by favorable electrostatic interactions (hydrogen bonds) of urea with the peptide backbone. There is no evidence for significant changes in hydrophobic interactions in the two conformations of the peptide in urea solution. Our simulations suggest that urea denatures proteins by preferentially forming hydrogen bonds to the peptide backbone, reducing the barrier for exposing protein residues to the solvent, and reaching the unfolded state.
KW - Computer simulations
KW - Denaturation
KW - Electrostatic interactions
KW - Hydrophobicity
KW - Potential of mean force
KW - Unfolding
UR - http://www.scopus.com/inward/record.url?scp=0037343333&partnerID=8YFLogxK
U2 - 10.1002/bip.10290
DO - 10.1002/bip.10290
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C2 - 12601795
AN - SCOPUS:0037343333
SN - 0006-3525
VL - 68
SP - 359
EP - 369
JO - Biopolymers
JF - Biopolymers
IS - 3
ER -