title: Conformations of phenylalanine in the tripeptides AFA and GFG probed by combining MD simulations with NMR, FTIR, polarized Raman, and VCD spectroscopy.
abstract: Conformational properties of small, flexible peptides are a matter of ongoing interest since they can be considered as models for unfolded proteins. However, the investigation of the conformations of small peptides is challenging as they are ensembles of rapidly interconverting conformers; moreover, the different methods used are prone to different approximations and errors. In order to obtain more reliable results, it is prudent to combine different techniques; here, molecular dynamics (MD) simulations together with nuclear magnetic resonance (NMR), Fourier transform IR (FTIR), polarized Raman, and vibrational circular dichroism (VCD) measurements were used to study the conformational propensity of phenylalanine in the tripeptides AFA and GFG, motivated by the relevance of phenylalanine for the self-aggregation of peptides. The results of this analysis indicate that the F residue predominantly populates the beta-strand (beta) and polyproline II (PPII) conformations in both AFA and GFG. However, while phenylalanine exhibits a propensity for beta-strand conformations in GFG (0.40 < or = beta population < or = 0.69 and 0.29 < or = PPII population < or = 0.42), the substitution of terminal glycines with alanine residues induces a higher population of PPII (0.31 < or = beta population < or = 0.50 and 0.37 < or = PPII population < or = 0.57).
authors.affiliation: Istituto per i Processi Chimico Fisici, Consiglio Nazionale delle Ricerche, Area della Ricerca di Pisa, via G. Moruzzi, 1 56124 Pisa, Italy. silvia.pizzanelli@ipcf.cnr.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Pizzanelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Forte
authors.forename: Susanna
authors.initials: S
authors.lastname: Monti
authors.forename: Giorgia
authors.initials: G
authors.lastname: Zandomeneghi
authors.forename: Andrew
authors.initials: A
authors.lastname: Hagarman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Measey
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schweitzer-Stenner
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman
chemical_list: D009842:Oligopeptides; D010649:Phenylalanine