ABSTRACT
As a result of this delicate balance only minor shifts in the contributions of any of these opposing forces can in principle significantly alter the stability of a protein. The small marginal stability of the native state, and the fact that these forces are cooperative and highly dependent on environmental conditions, such as temperature and solvent exposure, make the accounting of the contributions of these different forces to the stability of a protein a highly difficult task. Partially because of the uncertainty in the magnitude of these different interactions, the free energy of stabilization for a protein cannot be calculated, even if high-resolution crystal structure for the protein is available (1). Furthermore, such calculations based on atomic coordinates from crystal structures do not consider the dynamics of protein structures, a prerequisite for their function (1). Biologically active proteins such as enzymes are dynamic molecules and need a certain degree of structural flexibility for performing their function as biocatalysts (13-15).
