Effect of solute-solvent interactions on protein stability and ligand binding
Bibliographic record
Abstract
My doctoral thesis is aimed at characterizing the effect of solute–solvent interactions on protein stability and ligand binding events. To quantify non-specific protein–solvent interactions, we measured and analyzed partial molar volume and compressibility of proteins within a framework of statistical thermodynamic formalisms. We characterized the binding of tri-N-acetylglucosamine [(GlcNAc)3] and cAMP to lysozyme and cAMP-binding domain of EPAC1, respectively. Our volumetric measurements reveal that the protein–ligand complexes are less dynamic compared to their unbound states while complex formation is accompanied by the release of water of hydration to the bulk. To characterize protein–urea interactions, we determined and analyzed volumetric properties of four globular proteins at urea concentrations ranging from 0 to 8 M. We interpreted urea-dependent volumetric measurements in terms of the solvent exchange model in which the binding of urea to a protein proceeds with a release of two waters of hydration. Comparison of urea-dependent volumetric data for a folded protein with the similar data obtained on small molecules mimicking protein groups suggests the lack of cooperative effects involved in protein–urea interactions. Changes in volumetric properties associated with urea-induced unfolding transitions are consistent with solvent-accessible surface areas of unfolded proteins being roughly twice as large as those of their respective native states. Specifically, we reported the first experimental characterization of the thermodynamic profile of urea binding to a native protein. We measured the volumetric parameters of lysozyme as a function of urea within a temperature range of 18 to 45 ◦C. Based on the van’t Hoff analysis of the temperature dependence of the equilibrium constants for protein–urea binding events we evaluated the full thermodynamic profile of protein–urea interactions. Finally, we combined the experimental and theoretical approaches to investigate the influence of the urea on the binding of (GlcNAc)3 to lysozyme. Analysis of urea dependence of the binding free energy reveals that the protein–ligand binding reaction is governed by a close interplay between the free energy contributions of the excluded volume effect and direct solute–solvent interactions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".