This dissertation has discussed some of the many forces that make small and conflicting contributions to protein stability. It is the sum of these various stabilising and destabilising interactions that gives rise to the final stability of a protein. The total destabilising and the total stabilising energies are both large, and their difference is small. This is one of the reasons that current computational methods struggle to predict protein stability from structure.
Furthermore, our understanding of these many forces is incomplete; as often as not mutations have the opposite effect to that which had been predicted. In addition, the activation energy for folding is an important determinant of both kinetic stability and whether a protein will fold to a global minimum. However, it also clear that great strides have been made, and the search for the solution to The Folding Problem, one of the great remaining questions in biology, is and continues to be, an exciting one.
The chapter by Murphy particularly addresses the important thermodynamic principles behind protein stability. Dill provides a more general overview of the subject, presenting clearly both historical background and recent developments.
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Evolution and Stability Beginning
I would like to acknowledge the assistance of Jane Clark with text preparation and HTML. Any mistakes remaining are mine.