The interaction of thiocyanate with peptides-A computational study

Area of Science:

• Biochemistry
• Chemical Physics
• Computational Chemistry

Background:

• The Hofmeister series ranks ions by their effect on protein solubility and stability.
• Thiocyanate is identified as the strongest 'salting in' anion, exhibiting significant denaturant activity.
• A molecular-level understanding of the Hofmeister series and thiocyanate's denaturing mechanism is lacking.

Purpose of the Study:

• To investigate the molecular interactions of thiocyanate with polypeptide chains.
• To provide a computational basis for understanding thiocyanate's denaturing activity.
• To elucidate the role of direct ion-polypeptide interactions in protein denaturation.

Main Methods:

• Density functional theory (DFT) computational approaches were employed.
• Analysis of interactions between thiocyanate and various polypeptide groups (polar and nonpolar).
• Evaluation of hydrogen bonding and van der Waals forces.

Main Results:

• Thiocyanate directly interacts with both polar and nonpolar groups of polypeptide chains.
• Thiocyanate forms hydrogen bonds using both its nitrogen and sulfur atoms.
• Strong van der Waals interactions are observed between thiocyanate and nearly all polypeptide groups, irrespective of polarity.

Conclusions:

• Computational results support experimental findings of direct thiocyanate-polypeptide interactions.
• The ability of thiocyanate to interact broadly across the polypeptide chain explains its potent denaturing effect.
• This study offers a molecular-level insight into the mechanism of thiocyanate-induced protein denaturation.