Flogging nature’s tricks: the rational design of cooperativity

Flogging nature’s tricks: the rational design of cooperativity

Flogging nature’s tricks: the rational design of cooperativity (#8)

Kevin W Plaxco ¹ , Anna J Simon ¹

University of California Santa Barbara, Santa Barbara, CA, United States

Nature has evolved a large bag of “tricks” by which she can optimize the responsiveness of biomolecular receptors to small changes in target concentration. The increasing number of artificial biotechnologies reliant on biomolecular recognition could similarly profit from improved sensitivity, but efforts to engineer naturally occurring regulatory mechanisms, such as Hill-type cooperativity, into the receptors used in these technologies remain quite limited. In my talk I describe the use of intrinsic-disorder as a straightforward and rational means of quantitatively introducing cooperativity into normally non-cooperative receptors, achieving in the best of our examples Hill coefficients within error of the theoretical maximum. The approach, which appears general and can be implemented without detailed knowledge of a receptor’s structure, leads to significantly improved sensitivity.

Simon, A., Vallée-Bélisle, A., Ricci, F., and Plaxco, K.W. (2014) “Intrinsic disorder as a generalizable strategy for the rational design of highly responsive, allosterically cooperative receptors.” Proc. Nat. Acad. Sci. USA, 111, 15048–15053

Authors contributing to this presentation.

Plaxco, K.W

Kevin Plaxco is a Professor at the University of California, Santa Barbara, with a shared appointment between the Department of Chemistry and Biochemistry and the Biomolecular Science and Engineering graduate program. Prof. Plaxco also serves as Associate Director of campus’s Center for Bioengineering. Prior to joining UCSB in 1998 Dr. Plaxco received his Ph.D. from Caltech and performed postdoctoral studies at Oxford and the University of Washington. Dr. Plaxco’s research focus is on the physics of biomolecular folding and its engineering applications. A major aim of the group’s applied research is to harness the speed and specificity of folding in the development of sensors, adaptable surfaces, and smart materials. Dr. Plaxco has co-authored numerous patents and more than 170 papers on protein folding, protein dynamics, and folding-based sensors and materials, and in 2014 was recognized by Thomson Reuters at one of the most highly cited chemists of the last decade. He has also written a popular science book on Astrobiology.

Flogging nature’s tricks: the rational design of cooperativity (#8)

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Plaxco, K.W

Simon, A.J

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