Solid model compounds and the thermodynamics of protein unfolding

Area of Science:

• Physical Chemistry
• Biophysics
• Protein Thermodynamics

Background:

• Understanding protein stability is crucial for comprehending biological function.
• Previous models of protein denaturation often overemphasized the hydrophobic effect.
• Enthalpy and entropy convergence temperatures provide insights into thermodynamic contributions.

Purpose of the Study:

• To analyze thermodynamic data of cyclic dipeptide dissolution using group additivity.
• To explain enthalpy and entropy convergence temperatures in protein denaturation and compound dissolution.
• To assess the quantitative effects of hydrogen bonding and configurational effects on protein stability.

Main Methods:

• Analysis of thermodynamic data for solid cyclic dipeptides dissolving in water.
• Application of group additivity principles to thermodynamic data.
• Evaluation of apolar, hydrogen bonding, and configurational contributions to thermodynamic values.

Main Results:

• Apolar contributions to enthalpy and entropy changes are zero at convergence temperatures (TH* and TS*).
• Denaturational heat capacity includes large positive apolar and negative polar group contributions.
• Hydrogen bonding from peptide groups provides significant enthalpic stabilization, challenging liquid hydrocarbon models of the hydrophobic effect.

Conclusions:

• Protein thermodynamic properties can be predicted using average structural features (residue count, buried apolar groups, hydrogen bonds) and group contributions.
• Predicted thermodynamic values for cytochrome c, myoglobin, ribonuclease A, and lysozyme align well with literature data.
• The number of peptide and apolar groups are key determinants of a protein's major thermodynamic features.