The interest in finding the keys to the thermal stabilization of proteins has remained constant and unquestionable throughout the last twenty years. This article reviews the most recent theoretical and computer advances related to the problem of thermally stabilizing proteins. Although comparison between mesophilic and thermophilic sequences has suggested some thermostabilization mechanisms, it has not been able per se to provide unambiguous thermostabilization rules applicable for every case. Two of the mechanisms used by nature are seen as the major factors governing thermostability: the electrostatic forces of charged amino acids within a protein and the packing of its hydrophobic core on the other. Other mechanisms that have also been implicated (i.e. hydrogen bonding, α-helix stabilization, backbone rigidifying, etc), may play a refining role, based on the principle that nature has punctually and opportunistically thermostabilized proteins in each particular case, thereby solving each specific problem. How electrostatic and hydrophobic forces affect each other is still remains a largely open question and some recently developed criteria based on these two effects have been analyzed in the review.
Keywords: Protein thermostability, mesophiles, thermophiles, electrostatics, hydrophobicity, algorithms, theory
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