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Molecular Basis of Protein Adaptation to Harsh Environments: Rational Protein Design.

Restricted molecular mobility and reaction kinetics hinder myriad cellular and biomolecular processes in cold temperature environments. Psychrophiles and the enzymes they possess have adapted a variety of approaches to address this issue. The mechanisms for psychrophilic adaptability include the production of anti-freeze and cold shock proteins, alterations in membrane composition and overexpression of proteins that destabilize DNA. Additionally, psychrophilic enzymes have increased structural flexibility in their enzymes in comparison to their mesophilic couterparts (B-factor comparison of X-ray structures from psychrophiles and mesophiles).

We have found that there is a strong correlation between the extent of sidechain packing in a protein core and its thermostability. Specifically, we have shown that the cavity properties in psychrophilic enzymes endow these proteins with the enhanced conformational flexibility necessary to generate optimal activity at cold temperatures. Our studies indicated that the average cavity size (identified using CASTp at varying pore sizes) is larger in psychrophiles than in mesophiles and contains more hydrophilic residues. These cavities (1.4 -1.5 Å) can trap water molecules. The presence of cavities containing water within the protein core along with weaker side chain interaction between residues within the enzyme core increases the enzyme conformational dynamics of psychrophilic enzymes and contributes to their high activity levels observed in cold environments. This study provides an approach that can be employed for optimal temperature acquisition.

Figure 1. Flowchart methodology of pipeline algorithm used to build the psychrophilic with homologous protein dataset.



  1. D.I. Paredes, K. Watters, D.J. Pitman, C. Bystroff, and J.S. Dordick (2011), “Comparative Void-Volume Analysis of Psychrophilic and Mesophilic Enzymes: Structural Bioinformatics of Psychrophilic Enzymes Reveals Sources of Core Flexibility”, BMC. Struct. Biol. 11, 42.