Protein Conformational Transitions as Seen from the Solvent: Magnetic Relaxation Dispersion Studies of Water, Co‐solvent, and Denaturant Interactions with Nonnative Proteins

Hydration Dynamics in a Partially Denatured Ensemble of the Globular Protein Human α-Lactalbumin Investigated with Molecular Dynamics Simulations

“…dramatically during the N/MG transition, there would have to be a corresponding decrease in r s to compensate for it; in the case of HaLA, this would be a nearly 35% decrease for the scenario discussed above. For larger proteins, which allow a greater influx of water molecules, the decrease would be even more drastic (77). Such an interpretation of the NMRD data, although it is apparently consistent with the conclusions of the previously mentioned studies (13,56), appears counterintuitive when viewed in light of arguments put forward in a comprehensive review on protein conformational transitions, solvation, and the NMRD technique (77).…”

“…This information, combined with the observation of a 1.42-fold increase in the hydrodynamic (Stokes) radius, has been translated to an influx of 270 water molecules into the interior of the protein during the transition (56). The hydration number of a-lactalbumin has been estimated to be in the vicinity of 500 from the total surface area of the protein crystal structure (18,77), and hence, the calculated data imply an MG surface ;55% more hydrated than the N state. Such a large increase in hydration has also been proposed in 1 H NMR and spin diffusion studies of the N/MG transition in the larger carbonic anhydrase B protein (13).…”

Biophysical Characterization of Structural Properties and Folding of Interleukin-1 Receptor Antagonist

“…[44][45][46] This is particularly interesting because the mechanism of protein-denaturant interactions is the subject of much discussion, questioning whether it simply represents weak binding of denaturant molecules to specific protein sites 47,48 or whether it is dominated by indirect changes in solvent properties as in the transfer or linear free energy models. [49][50][51][52][53][54][55] The available data suggest a weak binding of urea to denatured proteins with widely varied estimates of K d and the observed variability likely reflects the existence of multiple denaturant binding sites with different affinities characteristic of disordered conformations.…”

Time Scales of Conformational Gating in a Lipid-Binding Protein

“…32,33 As noted above, this leads to lower and upper bounds on the MST of ∼10 ns and several μs. The two previous MRD studies of LBPs only examined protein solutions and could therefore not determine MSTs longer than ∼10 ns.…”

“…33,42 The contribution to R 1 k (ω 0 ) from internal motions in the hydration site, typically on a sub-picosecond time scale, was neglected in eq 2 since N k ≪ N H . Equation 1 is strictly valid only when the MST in site k is sufficiently short that the fast-exchange condition R 1 k (0)τ S,k ≪ 1 is fulfilled.…”