title: In silico interpretation of cw-ESR at 9 and 95 GHz of mono- and bis- TOAC-labeled Aib-homopeptides in fluid and frozen acetonitrile.
abstract: In this paper, we address the interpretation of molecular properties of selected singly and doubly spin-labeled peptides from continuous-wave electron spin resonance (cw-ESR) spectroscopy. This study is performed by means of an integrated computational approach that merges a stochastic treatment of long-term dynamics to ad hoc methodologies for the calculation of structural properties. In particular, our method is based on (i) the determination of geometric and local magnetic parameters of the peptides by quantum mechanical density functional calculations by taking into account solvent contribution; (ii) the hydrodynamic evaluation of dissipative properties; and (iii) molecular dynamics including equilibrium distribution of molecular conformations. The system is then described by a stochastic Liouville equation in which the spin Hamiltonian for the two electron spins, interacting with each other and coupled to two (14)N nuclear spins, is coupled to the diffusive operator describing the time evolution of slow coordinates. cw-ESR spectra are simulated for selected peptides built from the non-natural α-aminoacids α-aminoisobutyric acid (Aib) and 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC). In particular, we study the -Aib-TOAC-Aib- singly labeled tripeptide and the -Aib-TOAC-(Aib)(7)- singly labeled and -Aib-TOAC-(Aib)(5)-TOAC-Aib- doubly labeled nonapeptides. We show that good agreement is obtained with minimal resorting to fitting procedures, proving that the combination of sensitive ESR spectroscopy and sophisticated modeling is a powerful approach to the investigation of both molecular dynamics and 3D-structural properties.
authors.affiliation: Department of Chemistry, University of Padova, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carlotto
authors.forename: Mirco
authors.initials: M
authors.lastname: Zerbetto
authors.forename: Maryam Hashemi
authors.initials: MH
authors.lastname: Shabestari
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretto
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.forename: Martina
authors.initials: M
authors.lastname: Huber
authors.forename: Antonino
authors.initials: A
authors.lastname: Polimeno
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000621:Aminoisobutyric Acids / Q000737:chemistry*; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005615:Freezing; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013113:Spin Labels; D014961:X-Ray Diffraction
chemical_list: D000097:Acetonitriles; D000621:Aminoisobutyric Acids; D003497:Cyclic N-Oxides; D009842:Oligopeptides; D013113:Spin Labels; C100049:2-aminoisobutyric acid; C037109:2,2,6,6-tetramethylpiperidine-N-oxide-4-amino-4-carboxylic acid; C032159:acetonitrile