Water rotation barriers on protein molecular surfaces

Abstract

The experimental characterization of hindered-rotation barriers and mapping the energetic heterogeneity of water molecules bound to the molecular "surface" of proteins is critical for understanding the functional interaction of proteins with their environment. Here, we show how to achieve this goal by an original wide-line NMR procedure, which is based on the spectral motional narrowing phenomenon following the melting (thawing) process of interfacial ice. The procedure highlights the differences between globular and intrinsically disordered proteins and it enables to delineate the effect of solvent on protein structure, making a distinction between point mutants, monomeric and oligomeric states, and characterizing the molecular interactions taking part in different cellular processes. We put this unique experimental approach introducing novel physical quantities and quantifying the heterogeneous distribution of motional activation energy of water in the interfacial landscape into a historical perspective, demonstrating its utility through a variety of globular and disordered proteins.

Retracted: Molecular Motions and Interactions in Aqueous Solutions of Thymosin‐β4, Stabilin C‐Terminal Domain (CTD) and Their 1:1 Complex Studied by 1H NMR Spectroscopy

“…The strategic objective of our work is the thermodynamic characterization of protein molecules beyond their architectural, static description. The attributes introduced in works, moreover, the experimental results reported in Ref. and complemented here, are made use of in the thermodynamic characterization of the studied proteins.…”

“…Weak binding was confirmed between Tβ 4 and stabilin CTD and it was suggested that the proteins become slightly more disordered in the complex . Considerable progress has been achieved in several questions of the interpretation of wide line NMR results since relevant references were published . It was realized that the hydrogen nuclei in the water molecules with connection to the proteins act as magnetic probes which are integral parts of the material under investigation.…”

The impact of water on the ambivalent behavior and paradoxical phenomenon of the amyloid-β fibril protein

“…Among others, it delineates the bounded water's movements, reveals the monomeric and oligomeric protein states and also identifies the amyloid molecules in pathological processes. Although, the Aβ 42 fibril and the other disordered/ordered proteins are thermodynamically different, as only the amyloid protein is stable, this versatile NMR-method is also applicable for amyloids (41). Gáspári and Perczel (42) published an interesting and important review of a highly advanced NMR theory/ technique, in a book chapter.…”

“…Based on this phenomenon a sophisticated wide-line NMR procedure was developed by the Tompa's team with several purposes (41). Among others, it delineates the bounded water's movements, reveals the monomeric and oligomeric protein states and also identifies the amyloid molecules in pathological processes.…”

“…Considering the calculated binding energies [(tagged potential energy (TPE) (U TPE )] of the hydration water according to the segments are as follows: As a reference, the average TPE of the pure bulk water is −19.7 kcal mol The extracellular Aβ 40 and Aβ 42 fibril peptides Petkova and coworkers (28) studied in detail the molecular structure of the Aβ 40 fibril protein using the solid NMR technique, and also using X-ray fiber diffraction, transmission electron microscopy and MD simulations. Although this molecule is missing the Ile and Ala amino acid (41)(42) residues: the C-terminal part of the Aβ 42 fibril protein, does not make any essential difference in the structure and or in the conformation. [The hydropathy indices are: Ile = 4.5; Ala = 1.8 (23).…”