Protein design substrate specificity changes

Finally, another critical aspect for rapid and predictive design is the lack of information available about the dynamics of these enzymatic systems. Prediction of the effect of a mutation on the enzyme structure and dynamics remains a difficult task. Molecular dynamics and simulations of protein and substrate motions combined with the use of biophysical techniques enabling conformational changes to be trapped have to be developed. Multidisciplinary approaches will undoubtedly lead to major advances in this field and help to promote the key role that computational methods must play for efficient re-engineering of enzymes. These new ways to accelerate the evolution process and identify mutation sites important for optimizing enzyme characteristics will help to provide rapidly a well-expressed, efficient, stable, and specific enzyme, in other words the ideal glucansucrase for biocatalysis. 

Molecular modeling is also used in protein engineering to modify specifically or randomly selected residues of a protein to change the substrate specificity or to try to find an amino acid sequence that will fold into a specific, preselected 3D shape (the inverse protein folding problem). An introduction to this topic has been written by van Gunsteren. xhe principles of modeling have also been used to design new enzymes with altered substrate specificity. - ... 

The design of most protein probes involves the incorporation of a molecular substrate as a pendant into a metal complex. The recognition of the substrate by the protein host is then revealed by changes of the photophysical properties of the probe. However, metal complexes without a specific molecular substrate have also been employed the recognition is usually on the basis of hydrophobic interactions. As can be seen in the examples mentioned in Sect. 4, the hydrophobic nature of protein matrix, in particular the substrate-binding sites, provides opportunities in the development of new probes. 

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