Publication: An Effective Solvent Theory Connecting the Underlying Mechanisms of Osmolytes and Denaturants for Protein Stability
All || By Area || By Year| Title | An Effective Solvent Theory Connecting the Underlying Mechanisms of Osmolytes and Denaturants for Protein Stability | Authors/Editors* | Apichart Linhananta, Shirin Hadizadeh, Steven Samuel Plotkin |
|---|---|
| Where published* | Biophysical Journal |
| How published* | Journal |
| Year* | 2011 |
| Volume | 100 |
| Number | |
| Pages | 459-468 |
| Publisher | Biophysical Society |
| Keywords | protein folding, osmolytes, urea, cooperativity |
| Link | |
| Abstract |
An all-atom Go o model of Trp-cage protein is simulated using discontinuous molecular dynamics in an explicit minimal solvent, using a single, contact-based interaction energy between protein and solvent particles. An effective denaturant or osmolyte solution can be constructed by making the interaction energy attractive or repulsive. A statistical mechanical equiv- alence is demonstrated between this effective solvent model and models in which proteins are immersed in solutions consisting of water and osmolytes or denaturants. Analysis of these studies yields the following conclusions: 1), Osmolytes impart extra stability to the protein by reducing the entropy of the unfolded state. 2), Unfolded states in the presence of osmolyte are more collapsed than in water. 3), The folding transition in osmolyte solutions tends to be less cooperative than in water, as deter- mined by the ratio of van ât Hoff to calorimetric enthalpy changes. The decrease in cooperativity arises from an increase in native structure in the unfolded state, and thus a lower thermodynamic barrier at the transition midpoint. 4), Weak denaturants were observed to destabilize small proteins not by lowering the unfolded enthalpy, but primarily by swelling the unfolded state and raising its entropy. However, adding a strong denaturant destabilizes proteins enthalpically. 5), The folding transition in dena- turant-containing solutions is more cooperative than in water. 6), Transfer to a concentrated osmolyte solution with purely hard-sphere steric repulsion signiï¬cantly stabilizes the protein, due to excluded volume interactions not present in the canonical Tanford transfer model. 7), Although a solution with hard-sphere interactions adds a solvation barrier to native contacts, the folding is nevertheless less cooperative for reasons 1â3 above, because a hard-sphere solvent acts as a protecting osmolyte. |
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