Effect of glycine betaine on the hydrophobic interactions in the presence of denaturant: A molecular dynamics study

Abstract

Hydrophobic interactions are very important in a variety of systems such as proteins. Osmoprotectant glycine betaine (GB) stabilizes proteins against denaturation and counteracts harsh conditions such as presence of high concentration of urea. Therefore, it is interesting to specifically investigate the effect of osmolytes on hydrophobic interactions to explore whether the latter plays any role in the counteraction of denaturing property of urea. In this work, molecular dynamics simulations have been performed on neopentane (NEP), a non-polar molecule, in aqueous GB, urea, and GB-urea mixture to understand the effect of GB on hydrophobic interactions in the presence of urea. The results were analyzed by calculating radial distribution function, potential of mean force, coordination number, and interaction energies. The results indicate that the presence of GB decreases hydrophobic interactions between urea and NEP. We also find that GB and urea molecules strongly interact with each other through H bonding and electrostatic interactions. However, GB and urea have negligible effect on hydrophobic interactions between the NEP molecules. This study provides insights into the role of hydrophobic interactions in osmolyte induced counteraction of harsh conditions.