Dynamics of Hydrogen Bonds between Water and Intrinsically Disordered and Structured Regions of Proteins

Abstract

Recent studies indicate more restricted dynamics of water around intrinsically disordered proteins (IDPs) than structured proteins. We examine here the dynamics of hydrogen bonds between water molecules and two proteins, small ubiquitinrelated modifier-1 (SUMO-1) and ubiquitin-conjugating enzyme E2I (UBC9), which we compare around intrinsically disordered regions (IDRs) and structured regions of these proteins. It has been recognized since some time that excluded volume effects, which influence access of water molecules to hydrogen-bonding sites, and the strength of hydrogen bonds between water and protein affect hydrogen bond lifetimes. While we find those two properties to mediate lifetimes of hydrogen bonds between water and protein residues in this study, we also find that the lifetimes are affected by the concentration of charged groups on other nearby residues. These factors are more important in determining the hydrogen bond lifetimes than whether a residue hydrogen bonding with water belongs to an IDR or to a structured region.

Liquid–Liquid Phase Separation of the Intrinsically Disordered Domain of the Fused in Sarcoma Protein Results in Substantial Slowing of Hydration Dynamics

“…This figure demonstrates that the initial CLS is already somewhat higher for the condensate than for the homogeneous FUS LC from either FUS 12E or FUS LC at pH 11, indicating an enhanced amide I mode spectral inhomogeneity in the condensate. Incidentally, we also note that the starting value for the CLS is higher in FUS 12E (at pH 7.4) than in FUS LC at pH 11, suggesting distinct amide I spectral inhomogeneity under these conditions where FUS is homogeneous, consistent with the disordered nature of the protein and its malleability in different solution environments . We note that alternatively considering the nodal line slope gives similar results (Supplementary Figure 8).…”

“…Incidentally, we also note that the starting value for the CLS is higher in FUS 12E (at pH 7.4) than in FUS LC at pH 11, suggesting distinct amide I spectral inhomogeneity under these conditions where FUS is homogeneous, consistent with the disordered nature of the protein and its malleability in different solution environments. 49 We note that alternatively considering the nodal line slope gives similar results ( Supplementary Figure 8 ). In addition to the differing instantaneous ( T w = 0) inhomogeneity, the spectral dynamics differ markedly for the different protein states.…”

Intrinsic Disorder and Other Malleable Arsenals of Evolved Protein Multi-functionality

“…Instead, they have high amounts of polar and charged residues (Basu and Biswas, 2018;Már et al, 2023;Sun et al, 2013;Uversky, 2016a) which contribute to less sequence complexity in the absence of folding (Már et al, 2023;Uversky, 2016a). This results in partial temporal order by hydrogen bonding, water mediated contacts (indirect readouts) (Reid et al, 2023) and formation of transient interchangeable salt-bridges (Basu and Biswas, 2018). IDPs do not have a characteristic deep well in their energy landscapes like globular proteins, which means they do not conform to a lone stable 3D structure under physiological conditions.…”

Linear and Nonlinear Dielectric Response of Intrinsically Disordered Proteins

“…The NDE of IDPs has never been reported, and there are very few studies reported so far of the linear dielectric response of IDPs. , We start by focusing on the linear dielectric response of IDP solutions, followed with the analysis of the NDE. The linear frequency-dependent dielectric function of the solution is given in terms of the time autocorrelation function of the solution dipole moment. , The time scales of relaxation of the water and protein dipoles are widely separated, which allows us to look specifically at the time correlation function of the protein dipole.…”