title: The conformational ensemble of the β-casein phosphopeptide reveals two independent intrinsically disordered segments.
abstract: The β-casein phosphopeptide 1-25 (βCPP) is involved in calcium binding, cellular transduction, and dental remineralization. Though the net charge of 13e suggests an intrinsically disordered peptide, it has been shown to possibly maintain partial structure. To investigate the nature and extent of its conformational disorder, 100 independent molecular dynamics simulations (cumulative time of 30 μs) were conducted in explicit water with 0.1 M sodium chloride. βCPP adopted an ensemble of conformations (Rg = 8.61 ± 0.06 Å) stabilized primarily by ionic interactions and less so by hydrogen bonding (HB). Intramolecular contact maps showed a lack of interaction between the peptide's head (RELEELNVPGEIVEΣ) and tail (ΣΣΣEESITR) segments, suggesting their conformational independence. While many backbone HB interactions were observed between the amino acids in each segment, there was no persistent secondary structure evident. Our findings provide a framework for further investigation of βCPP's conformation and mechanism of action upon binding to calcium phosphate.
authors.affiliation: Department of Chemistry and Biology, Ryerson University , Toronto, Ontario M5B 2K3, Canada.
authors.forename: Muhammad Ali
authors.initials: MA
authors.lastname: Naqvi
authors.forename: Sarah
authors.initials: S
authors.lastname: Rauscher
authors.forename: Régis
authors.initials: R
authors.lastname: Pomès
authors.forename: Dérick
authors.initials: D
authors.lastname: Rousseau
mesh_terms: D000595:Amino Acid Sequence; D002364:Caseins / Q000737:chemistry*; D064267:Intrinsically Disordered Proteins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000737:chemistry; D017433:Protein Structure, Secondary
chemical_list: D002364:Caseins; D064267:Intrinsically Disordered Proteins; D010748:Phosphopeptides