Implications of protein flexibility for drug discovery

A large number of pharmaceutically relevant targets have been shown to be flexible, which are collected in this article. This comprehensive list of present and historical pharmaceutical targets provides the basis for questioning the relevance of the rigid receptor hypothesis, which is commonly used during in silico drug design.The role of protein flexibility in future pharmaceutical targets is likely to be even greater than in the past. Presently under-exploited target classes, such as ion channels, nuclear hormone receptors and transporters, have functions that are inextricably bound up with their structural flexibility.This article uses illustrative examples to discuss the implications of protein flexibility in drug discovery, and highlights how it could be exploited in drug design.