Small-molecule binding pockets

A predicted pocket may often have borderline characteristics just below a safe druggability threshold. In this case, exploring the conformational plasticity of the pocket (see Subheading 2.1.4) may help to find conformations more relevant for small-molecule binding. 

From a structural point of view, the nucleic acid receptor folds upon small molecule binding from a more or less disordered structure into a well-defined binding pocket, encapsulating the target. Numerous studies have shown that such structural reorganization of the functional nucleic acid, mediated by the small... 

The most extensive development of pharmacological inhibitors of MAPK cascades members has been for p38 (Table 1) [3]. Small-molecule inhibitors have been developed for two p38 isoforms (a and (3). Pyridinyl imidazole compounds have been known to block inflammation since the early 1970s. Structural analyses have revealed that p38 kinase inhibitors binds to the ATP-binding pocket of p38 thereby acting as competitive inhibitors. The p38 kinase inhibitor SB202190 is able to bind both the low-activity nonphosphorylated... 

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