Accurate secondary structure prediction and fold recognition for circular dichroism spectroscopy

TLDR

Circular dichroism spectroscopy is widely used for protein secondary structure analysis, yet quantitative estimation for β‑sheet–containing proteins is hindered by the morphological and spectral diversity of β‑structures. The authors present a general tool for rapid, reliable structure analysis with conventional or synchrotron CD spectroscopy, particularly useful when X‑ray or NMR methods are unavailable. By incorporating β‑sheet orientation and twist, the method accurately predicts secondary structure across diverse protein folds, especially β‑sheet‑rich proteins and amyloid fibrils, and can determine fold topology at the CATH level.

Abstract

Significance Circular dichroism (CD) spectroscopy is widely used for protein secondary structure analysis. However, quantitative estimation for β-sheet–containing proteins is problematic due to the huge morphological and spectral diversity of β-structures. We show that parallel/antiparallel orientation and twisting of β-sheets account for the observed spectral diversity. Taking into account the twist of β-structures, our method accurately estimates the secondary structure for a broad range of protein folds, particularly for β-sheet–rich proteins and amyloid fibrils. Moreover, the method can predict the protein fold down to the topology level following the CATH classification. We provide a general tool for a quick and reliable structure analysis using conventional or synchrotron radiation CD spectroscopy, which is especially useful when X-ray or NMR techniques fail.