| Details: |
Structure and function of proteins in aqueous medium can be altered by the presence of cosolvents such
as salts or osmolytes (osmoytes: small organic compounds which maintain cellular osmotic stress).
Denaturing osmolytes such as urea or denaturing salts such as guanidinium chloride (GdmCl)
destabilize the functional conformations of the cellular proteins. In contrast, protein protective
osmolytes such as trimethylamine N-oxide (TMAO) stabilize proteins’ native structures. In cellular
environment, proteins are exposed to mixtures of many cosolvents. In this talk, using molecular
dynamics simulation and the thermodynamical theory of solutions, I’ll discuss the stability and the
conformational changes of proteins in two biologically relevant cosolvent mixtures: a) urea-TMAO
(mixture of denaturing-protective osmolytes) and b) urea-GdmCl (mixture of two denaturants). First,
I’ll demonstrate how TMAO counteracts urea-denaturation by effectively removing urea from protein
surface. Then I’ll show how urea and GdmCl denature proteins via two distinctly different mechanisms
and how urea disfavors GdmCl-denaturation whereas GdmCl may potentially promote ureadenaturation
in mixed urea-GdmCl solutions. |