Antibodies affinity maturation

Macken and Perelson studied antibody affinity maturation as a random walk on the random energy landscape (Macken and Perelson, 1989 Macken et al., 1991 Macken and Perelson, 1991). The total number of mutants tried before a positive mutation is discovered T(F) is a measure of the change in the necessary size of the mutant library. The expected value of T, given that F is not a local optimum, is derived as... 

Directed evolution and antibody affinity maturation offer efficient routes to redesigning proteins for new functional characteristics. Adaptive mutations and well-defined selection pressures allow structural analysis of the evolved products to provide insights into the molecular basis of protein structure and function. It is interesting to note that the majority of mutations that were obtained in the present maturation and directed evolution experiments were located at positions away from the enzymatic active sites. Perhaps this is due to the inherent difficulty in retaining catalytic activity with most active site amino acid substitutions. 

Daugherty, P. S., Chen, G., Olsen, M. J., Iverson, B. L., and Georgiou, G. (1998). Antibody affinity maturation using bacterial surface display. Prot. Eng. 11, 101-108. 

Daugherty PS, Chen G, Olsen MJ, Iverson BL, Georgiou G. 1998. Antibody affinity maturation using bacterial surface display. Protein Engineering ll(9) 825-832. 

Doria-Rose NA, Joyce MG. Strategies to guide the antibody affinity maturation process. Current Opinion in Virology. 2015 11 137 7. 

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