Conformational analyses of peptides and proteins by vibrational Raman optical activity

Abstract

Recent developments of vibrational Raman optical activity (ROA) spectroscopy enabled the detailed analyses of the backbone and side chain conformations of peptides and proteins in solution phases. ROA can be used as a powerful analytical technique for determining not only the structures of conformers, but also their populations even for systems in fast conformational equilibria where NMR spectroscopy is difficult to be applied. ROA enabled the monitoring of the secondary structures of denatured or unfolded proteins, such as an amyloid fibril and its prefibril intermediates.

Recent advances in the use of vibrational chiroptical spectroscopic methods for stereochemical characterization of natural products

“…Density functional and basis set errors are expected to develop in any quantum mechanical calculation because it is based on approximations of atomic wave functions, the accuracy of such predictions being sensitive to the choice of the functional (either pure or hybrid), and directly proportional to the size of the basis set used. [53][54][55][56][57][58][59][60][61][62][63][64][65][66] In the following sections we will present examples of the application of VCD and ROA for stereochemical characterization of representative natural products. In liquid phase, solute-solvent interactions play an important role in the conformer geometry and population of exible molecules, mainly if experimental data in polar (H-bond forming) solvents need to be reproduced.…”

Conformational dynamics of carbohydrates: Raman optical activity of d-glucuronic acid and N-acetyl-d-glucosamine using a combined molecular dynamics and quantum chemical approach

“…[4][5][6][7][8][9] Whilst advances in instrumentation have led to the development of ROA, it has also greatly benefited from computational modelling. [4][5][6][7][8][9] Whilst advances in instrumentation have led to the development of ROA, it has also greatly benefited from computational modelling.…”

The Raman optical activity of β-d-xylose: where experiment and computation meet

“…[1][2][3] In particular, it offers an alternative to traditional analytical methods that are not always applicable. [4][5][6][7][8][9] ROA is the measurement of small differences in Raman scattering between circularly polarised light beams (incident, scattered or both). Since most biologically active molecules are chiral, ROA represents an attractive and powerful tool for the study of conformational dynamics, the structural elucidation of biological samples, and more generally the assignment of absolute configuration.…”

“…Because of its great sensitivity to molecular structure, sample conditions, or surrounding molecular environment, the interpretation of ROA experimental data greatly benefits from the support of modelling and simulation, nowadays well within common computational and theoretical means. [10][11][12][13] So far, ROA has mostly been applied to study peptide and protein structure 6,[14][15][16][17][18][19][20] while comparatively few efforts have been dedicated to carbohydrates, due to their flexibility and susceptibility to solvent effects. However, recent methodological developments [21][22][23] have put forward promising ways to tackle solvation modelling and conformational averaging.…”