Proteins stability prediction

Strohmeier W (1968) Problem und Modell der homogenen Katalyse. 5 96-117 Sugiura Y, Nomoto K (1984) Phytosiderophores - Structures and Properties of Mugineic Acids and Their Metal Complexes. 58 107-135 Sun H, Cox MC, Li H, Sadler PJ (1997) Rationalisation of Binding to Transferrin Prediction of Metal-Protein Stability Constants. 88 71-102 Swann JC, see Bray RC (1972) II 107-144... 

Because of the multiple degradation pathways that may take place at elevated temperature, protein stability monitoring data may not conform to the Arrhenius relationship, and the maximum temperature selected for accelerated stability studies must be carefully selected. Gu et al. [32] described the different mechanisms of inactivation of interleukin-1 (3 (IL-1 (3) in solution above and below 39°C. In this example, the multiple mechanisms precluded the prediction of formulation shelf life from accelerated temperature data. In contrast, by working at 40° C and lower, Perlman and Nguyen [33] were able to successfully extrapolate data from stability studies of tissue plasminogen activator down to 5°C. 

Structural factors are important regarding rational design approaches that lead to predicting stable protein folds. Can anything be learned about protein stability from different structural elements, amino acids, and packing of the native folds... 

The study of reaction rates or kinetics of a particular denaturation process of a protein therapeutic can provide valuable information about the mechanism, i.e., the sequence of steps that occur in the transformation of the protein to chemically or conformationally denatured products. The kinetics tell something about the manner in which the rate is influenced by such factors as concentration, temperature, excipients, and the nature of the solvent as it pertains to properties of protein stability. The principal application of this information in the biopharmaceutical setting is to predict how long a given biologic will remain adequately stable. 

Unfortunately, in spite of the published literature on wine proteins, we do not know the actual protein levels at which table or dessert wines are stable. The changes in protein content during production and processing of wines are still not known with sufficient accuracy to predict their behavior. The winemaker has to depend on empirical tests if he is to produce protein stable wines. Early separation of new wines from their fermentation yeast greatly improves their chances for protein stability by decreasing the release of yeast autolysis products into the wine. 

Helix stability and protein stability. We can predict the stability of helixes more reliably than we can any other element of protein structure. This provides a means for increasing the stability of proteins, because naturally occurring helixes are not always optimized for stability. If we make a mutation in the face of a helix that is exposed to solvent, and the mutation does not affect interactions elsewhere in the protein, then the overall free energy of folding of the protein generally changes by the same amount as the stability of the helix.47 This rule breaks down if we overstabilize the helix if the helix becomes so stable that it is still present as a helix in the denatured state, then increasing its stability further does not increase the stability of the protein, because both the native and denatured states are increased equally in stability. 

While the Hofmeister series and the Cohn-Edsall and Setschenow equations are useful tools for the estimation of protein stability and precipitation behavior, their usefulness is limited because of the lack of a quantitative relationship to molecular or solution properties. The goal of past and current efforts is to quantify the Hofmeister series and to predict the constants Ks and /3 (or Ks and log [E]0) in the Cohn-Edsall or Setschenow equations, respectively. Some of the most relevant efforts focus on ... 

Conclusion. In conclusion then it may be said that through this work we are moving towards a predictive mechanism for enzyme and water/stabilizer interactions which strengthen the structural relationship between the protein and its immediate environment, thus retaining its 3 dimensional structure. It is hoped that further research will lead to a full predictive model of the mechanism of enzyme stabilization and thus provide a completely generic protein stabilization system. 

Protein stability is the free energy difference (AG) between the folded and unfolded states at physiological conditions, and it is in the range of 5-25 kcal/mol. Site-directed mutagenesis experiments provided a wealth of data for understanding the importance of chemical interactions for the stability of proteins during amino acid substitutions. Protein stability is experimentally measured with differential scanning calorimetry, circular dichroism, fluorescence spectroscopy, and so forth. The availability of such data in an electronically accessible database would be a valuable resource for the analysis and prediction of protein mutant stability. 

The relationship between amino acid properties and protein stability revealed that the number of carbon atoms (methyl and methylene groups) that reflects the property hydrophobicity has a strong relationship with protein stability for the mutations in the interior of the protein. Yet, hydrophobic, hydrogen bond, electrostatic, and other polar interactions are important for the stability of mutation at the surface of the protein. The atom pair potentials set up on the basis of chemical nature and connectivity successfully could predict protein stability during amino acid substitution. 

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