Contribution of main chain and side chain atoms and their locations to the stability of thermophilic proteins

• Published in: Journal of molecular graphics & modelling Vol. 64; pp. 85 - 93
• Main Authors: Tompa, Dharma Rao, Gromiha, M.Michael, Saraboji, K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2016
• Subjects: Amino acid properties; Amino acids; Amino Acids - chemistry; Chains; Charging; Contact; Free energy; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Hydrophobic free energy; Mathematical models; Models, Molecular; Protein Conformation; Protein Stability; Proteins; Proteins - chemistry; Thermal stability; Thermodynamics; Thermophiles; Thermophilic proteins; Thermophilic proteins; Hydrophobic free energy; Amino acid properties; Thermal stability
• DOI: 10.1016/j.jmgm.2016.01.001
• ISSN: 1093-3263

[Display omitted] •Systematic structural study on larger dataset of thermophilic-mesophilic homologues.•Factors responsible for increased stability of thermophilic proteins are explored.•Hydrophobic free energy due to C, N+ and O atoms are stronger in thermophiles.•H-bonds in buried to exposed region, medium & long range contacts gives stability.•Large sidechain/charged residues results better free energy, packing and stability. Proteins belonging to the same class, having similar structures thus performing the same function are known to have different thermal stabilities depending on the source— thermophile or mesophile. The variation in thermo-stability has not been attributed to any unified factor yet and understanding this phenomenon is critically needed in several areas, particularly in protein engineering to design stable variants of the proteins. Toward this motive, the present study focuses on the sequence and structural investigation of a dataset of 373 pairs of proteins; a thermophilic protein and its mesophilic structural analog in each pair, from the perspectives of hydrophobic free energy, hydrogen bonds, physico-chemical properties of amino acids and residue–residue contacts. Our results showed that the hydrophobic free energy due to carbon, charged nitrogen and charged oxygen atoms was stronger in 65% of thermophilic proteins. The number of hydrogen bonds which bridges the buried and exposed regions of proteins was also greater in case of thermophiles. Amino acids of extended shape, volume and molecular weight along with more medium and long range contacts were observed in many of the thermophilic proteins. These results highlight the preference of thermophiles toward the amino acids with larger side chain and charged to make up greater free energy, better packing of residues and increase the overall compactness.