SESCA: Structure-based Empirical Spectrum Calculation Algorithm

Collaborations: Nykola Jones and Søren V. Hoffmann, ISA, Department of Physics & Astronomy, Aarhus University, DK

Funding: Alexander von Humboldt Foundation

Electronic circular dichroism (CD) spectroscopy is highly sensitive to changes in backbone structure of proteins, and does not require special labelling, crystallization, or high protein concentrations. Therefore, it is one of the first methods applied to characterize proteins, and can be combined with other methods such as stopped-flow techniques to study the kinetics and reaction mechanism of proteins. SESCA is a computational method that allows the rapid and accurate prediction of the CD spectra of protein models from their three-dimensional structure. SESCA predictions are based on two things: the secondary structure composition of the proposed protein models, and a set of pre-calculated basis spectra (basis set). The Basis spectra encode the average CD contribution of secondary structure elements, derived from the known structures and CD spectra of an experimental reference protein set.

SESCA calculations allow a direct comparison between the measured CD spectrum of a target protein and predicted CD spectra based a model structures or structural ensembles for determining the model quality. Although the CD spectrum of a typical globular protein can often be determined accurately from the secondary structure composition of its crystal structure, we applied several modifications to the original scheme to improve the prediction accuracy for short peptides and intrinsically disordered proteins. These modifications include scaling the spectrum intensity to account for normalization errors, basis spectra to address the contribution of amino acid side chains, and the use structural ensembles to account for protein flexibility and conformation heterogeneity.

SESCA Update

In our second publication (Nagy & Grubmüller, 2020), we focus on the accuracy and precision of structural circular dicrhoism based model validation methods with respect to experimental noise of the measured CD spectrum. This study allowes us to determine typical deviations between the secondary structure (SS) signal and the measured CD spectrum. The updated version of SESCA uses typical CD deviations to estimate the expected SS error of proposed protein models at a higher precision.

SESCA Software Package Zip File

Publication

Nagy, G.; Grubmüller, H.
How accurate are Circular Dicroism Based Secondary Structure Estimates?
biorxiv - preprint server for biology (2020)
Nagy, G.; Igaev, M.; Hoffmann, S. V.; Jones, N. C.; Grubmüller, H.: SESCA: Predicting circular dichroism spectra from protein molecular structures. Journal of Chemical Theory and Computation 15 (9), pp. 5087 - 5102 (2019)
Nagy, G.; Igaev, M.; Hofmann, S. V.; Jones, C. N.; Grubmüller, H.
SESCA: Predicting circular dichroism spectra from protein molecular structures
biorxiv - preprint server for biology (2019)
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