Theoretical (computational) modelling of complex protein-osmolyte interactions has always been challenging. Nowadays, computational power allows us to obtain numerically exact results for small to mid-size protein denaturation. But, are the current parameterizations of protein-osmolyte interactions reliable? This is difficult to answer without accurate experimental data to which we can benchmark our simulations. Our recent work in Journal of Physical Chemistry Letters, contributed to this important question on thermodynamic means.
We applied dialysis experiments on lysozyme protein and circular-dichroism on TrpCage miniprotein and quantified the depletion of protective osmolytes (TMAO, betaine) from protein surface.
On the computational side, we employed numerous parameterization of TMAO and betaine, which accurately reproduce experimental properties of aqueous solutions. Surprisingly, we have found that impact of stabilizing osmolytes on protein introduced in the solution can be very diverse. We could vaguely say, this stems from our belief that force-fields which perform well piece-wise, will perform well also when combined together. However, without careful readjustment of weak protein-osmolytes interactions, the simulation results can be even qualitatively wrong (i.e., observing protein denaturation).
This important theoretical message along with the urgent need for solid experimental data are presented in our concise letter, which is supported by an extensive SI 🙂
Computer modeling of complex systems 