Kinases conformational flexibility

Engh, Richard A. and Bossemeyer, D. (2002) Structural aspects of protein kinase control—role of conformational flexibility. Pharmacol. Therapeut. 93, 99-111. 

Dubey KD, Ojha RP (2012) Conformational flexibility, binding energy, role of salt bridge and alanine-mutagenesis for c-Abl kinase complex. J Mol Model 18(5)4679-1689... 

Nicklaus, M.C., Milne, G.W.A. and Burke, T.R. (1992). QSAR of Conformationally Flexible Molecules Comparative Molecular Field Analysis of Protein-Tyrosine Kinase Inhibitors. J.Comput.Aid.Molec.Des., 6,487-504. 

Using crystallographic studies we have been able to demonstrate that active anti-HIV compounds are capable of adopting unusual conformations. This shows that unusual conformational flexibility is an asset for activity and that the "active site" conformation of a nucleoside at the kinase is a special conformation. 

Protein kinases can exist in active and inactive forms, which is why they are able to perform the function of a switch in signaling pathways. Protein kinases are particularly suitable as switches in signal pathways due to their flexible structure of two domains that can adopt different orientations with respect to one another. Fmthermore, in the cleft between the two domains, it is possible to initiate signal-controlled conformational changes of great importance for substrate binding and catalytic activity. 

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