Protein Stability and Protein Folding

Protein stability is the net balance of forces which allow someone to tell whether or not the protein will be denatured. This is also referred to as thermodynamic stability. The net stability can be defined as the difference in free energy between the native and denatured state. These two values can be called Gn and Gu.

In the previous blog post, free energy was introduced as related to free energy. The Gibbs Free Energy value can be calculated using a variety of equations. In fact, there are four ways to calculate this value. The four ways include delta G = delta H - T (delta S), the difference between the free energies of products and reactants, Hess's Law, and delta G = delta Go + RTlnQ.

Decreasing the energy of the folded state or increasing the energy of the unfolded state have the same effect on delta G. The equation normally used to calculate the free energy can be taken from delta G = Gn - Gu = -RTlnK. In this case, the K would be equal to the fraction folded divided by the fraction unfolded. The reason why this practice has so much significance is because of the multitude of drugs that can be made if different proteins were seen as more stable. Various new formulas for different protein combinations can be made, which may be able to make them safer to sell in pharmacies.

We will take this formula and put it into good use through practice! We can measure the difference in free energy in the unfolded and folded states. The average stability of a monomeric small protein is about 5-10 kcal/mol. Therefore, when plugged into the equation, an aqueous solution at room temperature would have a ratio of 20000000:1 in terms of folded to unfolded. This value of K can also be looked at as the ratio of the forward and reverse rate constants. When delta G is graphed against Denaturant or Urea, the graph typically comes out to be downward sloping, signalling a drop in the amount of free energy changed.

The Van't Hoff Equation can also be written as dlnK/d(1/T) = -H/R. Thus, when Van'T Hoff plots (lnK vs. 1/T) are made, the thermal denaturation of proteins are non-linear, indicating that H varies with temperature. This implies that the heat capacity for the folded and unfolded proteins are different.