Structure and effect of sarcosine on water and urea by using molecular dynamics simulations: Implications in protein stabilization

Sarcosine is one of the most important protecting osmolytes which is also known to counteract the denaturing effect of urea. We used molecular dynamics simulation methods to investigate the mechanism of protein stabilization and counteraction of urea by sarcosine. We found that sarcosine enhanced the tetrahedral structure of water and strengthened its hydrogen bonding network. We also found that sarcosine did not form clusters unlike glycine. Our results show strong interaction between sarcosine and urea molecules. Addition of sarcosine enhanced the urea-water structure and urea-water lifetime indicated an increase in the solvation of urea. These findings suggest that sarcosine indirectly stabilizes protein by enhancing water-water structure thus decreasing the hydrophobic effect and counteracts the effect of urea by increasing the solvation of urea and directly interacting with it leaving urea less available to interact with protein.

Graphical abstractDownload full-size imageHighlights► MD simulations of sarcosine have been performed in water and in water + urea system. ► RDFs and SDFs were examined along with hydrogen bond dynamics. ► Results support indirect mechanism of protein stabilization. ► Sarcosine counteracts urea by increasing its solvation.