Protein engineering sequence-activity relationships

Protein engineering based on sequence-activity relationships is attractive because of the small numbers of variants that need to be tested in order to obtain improvement. In principle this frees the investigator from the tyranny of high throughput screening. It also allows one to design and create the most informative set of variants, rather than relying upon a stochastically constructed library (i-6). 

Figure L Protein engineering process using sequence activity relationships.

We have described a method for engineering proteins based on design, synthesis and testing of small numbers of iiulividual variants followed by mathematical modeling to determine a sequence-activity relationship. We have also shown that sequence-activity models can be used predictively to design improved variants. 

As stated in Chapter 9, The consilient approach to tissue engineering utilizes biology s own materials and mechanisms, concerned with tissue structure and function, to achieve tissue restoration. The key materials elements are three the capacity of the elastic protein-based material to match the elastic modulus of the tissue to be restored, a remarkable biocompatibility of the pure elastic protein-based material, and the facility to design into the protein-based polymer sequence any desired biologically active sequence, which, by virtue of the innocuousness of the elastic protein-based material, allows proper expression of the incorporated biologically active sequence. This provides the opportunity for the proper functional relationship of protein-based material to the cells and the extracellular matrix of the tissue to be restored. 

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