## Problem 092 — rank:136

**Title:** Hydration contribution to biomolecular stability

**Added binding assumptions (LaTeX):**

```latex
For a hydration contribution to folding, apply thermodynamic integration separately within the same folded and unfolded basins and subtract the two alchemical free-energy changes. One unrestricted ensemble integral instead gives the free-energy change of that whole ensemble, not automatically folding stabilization. Specify endpoint Hamiltonians and basin restraints; path-dependent attribution does not change the path-independent total between fixed endpoints.
```

**Direct edits:** 0. **Fresh external checks:** None; supplied sources retained as provenance.