title: Reactive molecular dynamics study of the pH-dependent dynamic structure of α-helix.
abstract: We have studied the α-helix to random coil transition using ReaxFF reactive molecular dynamics as a function of pH. Urea binding to peptides and associated interference with backbone H-bonds and charged side chains interactions, which can both denature the helices, have been studied previously using nonreactive force fields (Topol, I. A. J. Am. Chem. Soc. 2001, 123, 6054-6060). This study reveals new proton-transfer mechanisms related to the denaturation of α-helical structures, which cannot be captured by nonreactive molecular dynamics. In addition, we show that proton transfer between the solution and the peptide can break the α-helix hydrogen bonds, and consequently, at extreme pHs, a significant amount of helix will unravel. We also compare the effects of temperature in the denaturation mechanism. The ReaxFF findings are in significantly better agreement with ab initio calculations than previous nonreactive force field results, indicating the relevance of the reactive component on helical loss.
authors.affiliation: Department of Mechanical and Nuclear Engineering, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
authors.forename: M
authors.initials: M
authors.lastname: Golkaram
authors.forename: Y K
authors.initials: YK
authors.lastname: Shin
authors.forename: A C T
authors.initials: AC
authors.lastname: van Duin
mesh_terms: D000409:Alanine / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D011522:Protons; D013329:Structure-Activity Relationship; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D011522:Protons; D014867:Water; D000409:Alanine