INTRODUCTION: Protein thermostability is an important field for its evolutionary perspective of mesophilic versus thermophilic relationship and for its industrial/ therapeutic applications. METHODS: Presently, a total 400 (200 thermophilic and 200 mesophilic homologue) proteins were studied utilizing several software/databases to evaluate their @entity3689 preferences. Randomly selected 50 homologous proteins with available PDB-structure of each group were explored for the understanding of the protein charges, isoelectric-points, hydrophilicity, hydrophobicity, @entity4149 phosphorylation and salt-bridge occurrences. These 100 proteins were further probed to generate Ramachandran plot/data for the gross secondary structure prediction in and comparison between the thermophilic and mesophilic proteins. RESULTS: Present results strongly suggest that nonpolar smaller volume @entity1522 Ala (  2 = 238.54, p<0.001) and @entity4022 (  2 = 73.35, p<0.001) are highly and @entity2596 moderately (  2 = 144.43, p<0.001) occurring in the 85% of thermophilic proteins. Phospho-regulated Tyr and redox-sensitive @entity2569 are also moderately distributed (  2~20.0, p<0.01) in a larger number of thermophilic proteins. A consistent lower distribution of thermophilicity and discretely higher distribution of hydrophobicity is noticed in a large number of thermophilic versus their mesophilic protein homolog. The mean differences of isoelectric points and charges are found to be significantly less (7.11 vs. 6.39, p<0.05 and 1 vs. -0.6, p<0.01, respectively) in thermophilic proteins compared to their mesophilic counterpart. The possible sites for Tyr phosphorylation are noticed to be 25% higher (p<0.05) in thermophilic proteins. The 60% thermophiles are found with higher number of salt bridges in this study. The average percentage of salt-bridge of thermophiles is found to be higher by 20% than their mesophilic homologue. The GLU-HIS and @entity70136 salt-bridge dyads are calculated to be significantly higher (p<0.05 and p<0.001, respectively) in thermophilic and GLU- @entity534 is higher in the mesophilic proteins. The Ramachandran plot/ data suggest a higher abundance of the helix, left-handed helix, sheet, nonplanar peptide and lower occurrence of cis peptide, loop/ turn and outlier in thermophiles. Pearson's correlation result suggests that the isoelectric points of mesophilic and thermophilic proteins are positively correlated (r = 0.93 and 0.84, respectively; p<0.001) to their corresponding charges. And their hydrophilicity is negatively associated with the corresponding hydrophobicity (r = -0.493, p<0.001 and r = -0.324, p<0.05) suggesting their reciprocal evolvement. CONCLUSIONS: Present results for the first time with this large amount of datasets and multiple contributing factors suggest the greater occurrence of hydrophobicity, salt-bridges and smaller volume nonpolar residues ( @entity4022 , Ala and @entity2596 ) and lesser occurrence of bulky polar residues in the thermophilic proteins. A more stoichiometric relationship amongst these factors minimized the hindrance due to side chain burial and increased compactness and secondary structural stability in thermophilic proteins.

Protein Thermostability Is Owing to Their Preferences to Non-Polar Smaller Volume XXXX , Variations in Residual Physico-Chemical Properties and More Salt-Bridges.

@entity1522 :: ('CHEBI:33709', 'Chemical') :: ['amino acids'] @entity2569 :: ('CHEBI:17561', 'Chemical') :: ['Cys'] @entity70136 :: ('CHEBI:73521', 'Chemical') :: ['GLU-LYS'] @entity4022 :: ('MESH:C066286', 'Chemical') :: ['Gly'] @entity534 :: ('CHEBI:16467', 'Chemical') :: ['ARG'] @entity2596 :: ('CHEBI:16414', 'Chemical') :: ['Val'] @entity3689 :: ('D000596', 'Chemical') :: ['amino acid'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine']
@entity1522 :: (CHEBI:33709,Chemical) :: ['Amino Acids']
