title: Exploring atomistic details of pH-dependent peptide folding.
abstract: Modeling pH-coupled conformational dynamics allows one to probe many important pH-dependent biological processes, ranging from ATP synthesis, enzyme catalysis, and membrane fusion to protein folding/misfolding and amyloid formation. This work illustrates the strengths and capabilities of continuous constant pH molecular dynamics in exploring pH-dependent conformational transitions in proteins by revisiting an experimentally well studied model protein fragment, the C peptide from ribonuclease A. The simulation data reveal a bell-shaped pH profile for the total helix content, in agreement with experiment, and several pairs of electrostatic interactions that control the relative populations of unfolded and partially folded states of various helical lengths. The latter information greatly complements and extends that attainable by current experimental techniques. The present work paves the way for new and exciting applications, such as the study of pH-dependent molecular mechanism in the formation of amyloid comprising peptides from Alzheimer's and Parkinson's diseases.
authors.affiliation: Department of Molecular Biology, TPC6, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Khandogin
authors.forename: Jianhan
authors.initials: J
authors.lastname: Chen
authors.forename: Charles L
authors.initials: CL
authors.lastname: Brooks
mesh_terms: D019943:Amino Acid Substitution; D003198:Computer Simulation; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000502:physiology; D010455:Peptides / Q000737:chemistry* / Q000502:physiology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D010455:Peptides; C037001:ribonuclease A, C-peptide; D012259:Ribonuclease, Pancreatic