Induced Folding The Bete Noire of Drug Design

1 Induced Folding The Bete Noire of Drug Design 

Fernandez, Transformative Concepts for Drug Design Target Wrapping, 187 

However intractable, we are compelled to deal with this problem for a very simple reason the highest variability in amino acid composition across kinases occurs precisely in the floppy regions, more specifically in the activation loop [12]. Thus, the most significant specificity-promoting feature becomes in practice the most difficult to target  

As illustrated in this chapter, the induced folding problem may be tractable in special contexts that are relevant to drug design there are restrictive instances where structural adaptation may be steered in a controllable and predictable way, and selectivity control may be achieved through the identification of targets that undergo a similar induced fit upon association. 

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