Surface hydration and preferential interaction directs the charged amino acids-induced changes in protein stability

Area of Science:

• Biochemistry and Molecular Biophysics
• Protein Dynamics and Stability
• Biophysical Chemistry

Background:

• Amino acid osmolytes and denaturants modulate protein stability.
• Understanding these interactions is crucial for protein folding and function.

Purpose of the Study:

• Investigate the interaction mechanisms of charged amino acids (Arg, Lys, Asp, Glu) and guanidinium chloride (Gdm) with proteins.
• Elucidate the molecular basis of amino acid-induced protein stabilization and destabilization.

Main Methods:

• Molecular dynamics (MD) simulations of RNase A and α-lactalbumin.
• Analysis of radial distribution function and hydration fraction.
• Residue-level interaction analysis.

Main Results:

• All cosolvents increased preferential hydration, with stabilizing amino acids (Lys, Asp, Glu) showing a greater effect than destabilizing ones (Arg, Gdm).
• Arg and Gdm exhibited higher preferential interaction with proteins compared to stabilizing amino acids.
• Stabilizing amino acids preferentially interacted with charged protein residues, while Arg and Gdm interacted with most exposed residues.

Conclusions:

• The net balance between preferential hydration and preferential interaction dictates the effect of amino acids on protein stability.
• This study provides insights into the molecular mechanisms governing protein-ligand interactions and stability.