Molecular mechanisms underlying the effects of urea and the structural dynamics of bovine serum albumin.

Abstract

The disruption of protein structures by denaturants such as urea is well-documented, although the underlying molecular mechanisms are not yet fully understood. In this study, we employed molecular dynamics simulations to examine the effects of urea on the structural stability of bovine serum albumin (BSA) at concentrations ranging from 0 to 5M. Our results reveal that urea induces a dehydration-rehydration cycle by displacing and partially substituting water molecules in BSA's hydration shell. At lower concentrations, urea decreases protein-water hydrogen bonding while enhancing protein-urea interactions. At higher concentrations, urea tends to aggregate, which limits direct interactions with the protein, promotes rehydration, and leads to alterations in the tertiary structure, although the secondary structure remains largely preserved. These findings offer mechanistic insights into urea-induced protein denaturation and stability.