Theoretical Study of the Effective Chemical Shielding Anisotropy (CSA) in Peptide Backbone, Rating the Impact of CSAs on the Cross-Correlated Relaxations in l-Alanyl-l-alanine

Abstract

The dependence of the effective chemical shielding anisotropy (effective CSA, Δσ eff ) on the and ψ peptide backbone torsion angles was calculated in the L-alanyl-L-alanine (LALA) peptide using the DFT method. The effects of backbone conformation, molecular charge including the cation, zwitterion, and anion forms of the LALA peptide, and the scaling taking into account the length of the dipolar vector were calculated for the effective CSAs in order to assess their structural behaviors and to predict their magnitudes which can be probed for the -sheet and R-helix backbone conformations via measurement of the cross-correlated relaxation rates (CCR rates). Twenty different CSA-DD cross-correlation mechanisms involving the amide nitrogen and carbonyl carbon chemical shielding tensors and the C R H R (R-carbon group), NH N (amide group), C R H N , NH R , C′H R , and C′H N (R ) R1, R2) dipolar vectors were investigated. The X-C R H R (X ) N, C′; R ) R1, R2) cross-correlations, which had already been studied experimentally, exhibited overall best performance of the calculated effective CSAs in the LALA molecule; they spanned the largest range of values upon variation of the ψ and torsions and depended dominantly on only one of the two backbone torsion angles. The X-NH N (X ) N, C′) cross-correlations, which had been also probed experimentally, depended on both backbone torsions, which makes their structural assignment more difficult. The N-NH R2 and N-C′H R1 crosscorrelations were found to be promising for the determination of various backbone conformations due to the large calculated range of the scaled effective CSA values and due to their predominant dependence on the ψ and torsions, respectively. The 20 calculated dependencies of effective CSAs on the two backbone torsion angles can facilitate the structural interpretation of CCR rates.

Chiral sensing of amino acids and proteins chelating with EuIIIcomplexes by Raman optical activity spectroscopy

“…3 Their luminescence is particularly sensitive to the environment of the lanthanide metal; circularly polarized luminescence (CPL), difference in the emission of leftand right-circularly polarized light, provides additional information about molecular chirality, and is thus commonly employed in biologically oriented applications. [4][5][6][7] However, the development of molecular biologically relevant probes based on lanthanides is not straightforward. For example, many europium(III) complexes decompose in the aqueous environment 8 or the luminescence in water solutions is strongly affected by interaction with the O-H groups.…”

The Impact of Hydrogen Bonding on Amide 1H Chemical Shift Anisotropy Studied by Cross-Correlated Relaxation and Liquid Crystal NMR Spectroscopy

“…17,29 As indicated by DFT calculations, amide 15 N CSA is impacted by many variables, including backbone and side chain torsion angles, hydrogen bonding, and residue type. 30−32 We have recently shown(29) that 15 N CSA magnitudes of the third Igg binding domain of protein G (GB3, dissolved in a medium containing liquid crystalline Pf1) correlate well with those obtained from spinning sideband analysis of slow magic angle spinning (MAS) solid-state NMR measurements(17) on a closely homologous domain. Asymmetry of the CSA tensor was found to be dominated by the backbone torsion angles.…”

“…For example, for backbone 13 C′ nuclei in small proteins, accurate CSA values have been obtained by both solution and solid state NMR. , These results clearly confirmed prior results − which indicate that variation in isotropic 13 C′ chemical shifts can be attributed almost entirely to differences in the σ YY component of the shielding tensor. − The latter is a steep function of both backbone torsion angles and hydrogen bond strength. − For backbone amide 15 N, the range of isotropic shifts observed in proteins is large, spanning more than 20 ppm for residues of any given type, but both computational and empirical efforts to correlate chemical shift changes to structural parameters have been challenging. Much effort has been devoted to measuring the 15 N CSA tensor in proteins, ,− both by solution and solid-state NMR methods, but only recently has a consensus started to emerge. , As indicated by DFT calculations, amide 15 N CSA is impacted by many variables, including backbone and side chain torsion angles, hydrogen bonding, and residue type. − We have recently shown that 15 N CSA magnitudes of the third Igg binding domain of protein G (GB3, dissolved in a medium containing liquid crystalline Pf1) correlate well with those obtained from spinning sideband analysis of slow magic angle spinning (MAS) solid-state NMR measurements on a closely homologous domain. Asymmetry of the CSA tensor was found to be dominated by the backbone torsion angles.…”

Correlating the 31P NMR Chemical Shielding Tensor and the 2JP,C Spin–Spin Coupling Constants with Torsion Angles ζ and α in the Backbone of Nucleic Acids

“…The CSA–DD CCR is a NMR phenomenon resulting from the interference of the CSA and dipole–dipole (DD) relaxation mechanisms. , The CSA–DD CCR rates depend on mutual orientation of the CSA and DD interaction tensors and thus also on local molecular geometry. The so-called “remote” CSA–DD CCRs, which correlate CSA and DD interactions centered on different nuclei, were previously applied for determination of torsion angles in peptides , and NAs. ,,, Theoretical studies provided nonempirical insights into the geometry dependence of the CSA–DD CCR rates, including the effect of geometry dependence of the chemical shielding tensor. , …”

“…8,9,32,33 Theoretical studies provided nonempirical insights into the geometry dependence of the CSA−DD CCR rates, including the effect of geometry dependence of the chemical shielding tensor. 34,35 In this work, we focused on the remote CSA−DD crosscorrelation between the 31 P chemical shielding tensor and the adjacent C5′−H5′ dipolar vectors. According to the Redfield theory of relaxations, assuming invariable relative orientation of the CSA and DD principal axis frames, the remote transversal CSA−DD CCR rate Γ P,CH is given by 28,29 μ…”