JEFFREY K. MYERS¹*, SAUL R. TREVINO²
*Corresponding author
1. Davidson College Department of Chemistry Box 7120 Davidson, NC 28035-7120, USA
2. Houston Baptist University Department of Chemistry Houston, TX 77074, USA

Abstract

Most proteins fold to specific native conformations in order to function. Conformational stability is a thermodynamic quantity which reflects the population of protein in its native, functional state. We review strategies used to increase protein stability by altering the primary sequence or the protein’s environment. Globular protein stability is an important factor that can limit the usefulness of proteins as pharmaceuticals or in biotechnology applications.

INTRODUCTION

The usefulness of proteins utilized for biotechnological or pharmaceutical purposes may be limited by the conformational stability of the protein. To be functional, most proteins adopt specific folded structures that are thermodynamically stable; the thermodynamic stability of the native, folded conformation is termed “conformational stability”. Conformational stability can be defined as the difference in free energy between the native (folded, functional) state and all other conformational states that are in equilibrium with the native state (intermediates and the unfolded or denatured state):
where R is the gas constant, T is temperature in Kelvin, and the sum of [nonnative]i represents all other thermodynamic states of the protein besides the native state. Many simple proteins show only one other stable thermodynamic state besides the folded state, namely the denatured or unfolded state; these proteins will exhibit two-state unfolding behaviour. Throughout this review, we will refer to the free energy change in the unfolding direction, such that a positive value indicates a stable native state. (formula 1)
Protein stab ...