Role of hydrophobic side chain in urea induced protein denaturation at interface

Abstract

The molecular mechanism of denaturing ability of urea is still a subject of considerable debate due to two opposing mechanisms: direct and indirect. In the direct mechanism, urea directly disrupts hydrogen bonding and hydrophobic interactions within proteins. On the other hand, the indirect mechanism suggests that urea alters the properties of water and disrupts protein-protein interactions. Our aim is to unravel the denaturing mechanism of urea by studying its interaction with the side chain of octadecylphosphonic acid (ODPA)) as a mimicking surface of a protein. We employ vibrational sum frequency generation (VSFG) spectroscopy to examine the interaction between urea, the side chain of ODPA, and water molecules at the interface. Our findings suggest that urea interacts with the side chain of ODPA, effectively reducing the hydrophobic barriers provided by the long hydrophobic chain of the ODPA molecules for the water molecules at the interface. The interaction of the urea with the side chain of the ODPA molecules results in the alignment of water molecules, increasing their SFG intensity. Our findings indicate that the interaction of urea with the side chain plays a crucial role in governing the interaction between water and ODPA molecules. These outcomes help us understand the side chain's role in urea-induced protein denaturation at the interface.