Amino acid recognition for automatic resonance assignment of intrinsically disordered proteins

Abstract

Resonance assignment is a prerequisite for almost any NMR-based study of proteins. It can be very challenging in some cases, however, due to the nature of the protein under investigation. This is the case with intrinsically disordered proteins, for example, whose NMR spectra suffer from low chemical shifts dispersion and generally low resolution. For these systems, sequence specific assignment is highly time-consuming, so the prospect of using automatic strategies for their assignment is very attractive. In this article we present a new version of the automatic assignment program TSAR dedicated to intrinsically disordered proteins. In particular, we demonstrate how the automatic procedure can be improved by incorporating methods for amino acid recognition and information on chemical shifts in selected amino acids. The approach was tested in silico on 16 disordered proteins and experimentally on α-synuclein, with remarkably good results.Electronic supplementary materialThe online version of this article (doi:10.1007/s10858-016-0024-2) contains supplementary material, which is available to authorized users.

Linear discriminant analysis reveals hidden patterns in NMR chemical shifts of intrinsically disordered proteins

“…For this reason, we decided to facilitate the transfer by means of LDA. Using 1 H and 15 experimental peak positions, we peak picked the 4D HabCab(CO)NH spectrum, obtaining the H α , H β , C α and C β chemical shifts of the preceding residues. We then performed LDA on them (Fig.…”

“…In short, we can easily recognize alanine, glycine, serine and threonine, but more detailed analysis is needed for other amino acid residue types. Some of the above-mentioned recognition procedures are embedded in automatic assignment programs [13][14][15][16].…”

Enhancing Compression Level for More Efficient Compressed Sensing and Other Lessons from NMR Spectroscopy

“…They modified a CBCA(CO)NH pulse sequence [45], to acquire a signal for amino acid types selected basing on topology. Only desired amino acid residues give signals in such spectra, which facilitates the analysis and allows efficient low-level non-uniform sampling [46].…”

Proline Fingerprint in Intrinsically Disordered Proteins

“…A comment is due on the general applicability of the simple proline‐fingerprint strategy proposed here to the whole suite of C′ detected multidimensional NMR experiments used to study IDPs . This very straightforward modification can be easily included in any of the NMR experiments based on C′ detection that exploit the C′−N correlation.…”