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https://doi.org/10.3390/molecules201018732
14. Huse M, Kuriyan J (2002) The conformational plasticity of protein kinases. Cell 109:275–282.
https://doi.org/10.1016/s0092-8674(02)00741-9
15. Jacobs MD, Caron PR, Hare BJ (2007) Classifying protein kinase structures guides use of
ligand-selectivity profiles to predict inactive conformations: structure of lck/imatinib complex.
Proteins 70:1451–1460. https://doi.org/10.1002/prot.21633
16. Lee M, Balupuri A, Jung Y, Choi S, Lee A, Cho Y, Kang N (2018) Design of a novel and
selective IRAK4 inhibitor using topological water network analysis and molecular modeling
approaches. Molecules 23:3136. https://doi.org/10.3390/molecules23123136
17. Walter NM, Wentsch HK, Bührmann M, Bauer SM, Döring E, Mayer-Wrangowski S, SieversEngler A, Willemsen-Seegers N, Zaman G, Buijsman R, Lämmerhofer M, Rauh D, Laufer SA
(2017) Design, synthesis, and biological evaluation of novel type I(1)/2 p38α MAP kinase
inhibitors with excellent selectivity, high potency, and prolonged target residence time by
interfering with the R-spine. J Med Chem 60:8027–8054. https://doi.org/10.1021/acs.
jmedchem.7b00745
18. Ortuso F, Amato R, Artese A, D’antona L, Costa G, Talarico C, Gigliotti F, Bianco C,
Trapasso F, Schenone S, Musumeci F, Botta L, Perrotti N, Alcaro S (2014) In silico identification and biological evaluation of novel selective serum/glucocorticoid-inducible kinase
1 inhibitors based on the pyrazolo-pyrimidine scaffold. J Chem Inf Model 54:1828–1832.
https://doi.org/10.1021/ci500235f
19. Slynko I, Schmidtkunz K, Rumpf T, Klaeger S, Heinzlmeir S, Najar A, Metzger E, Kuster B,
Schüle R, Jung M, Sippl W (2016) Identification of highly potent protein kinase C-related
kinase 1 inhibitors by virtual screening, binding free energy rescoring, and in vitro testing.
ChemMedChem 11:2084–2094. https://doi.org/10.1002/cmdc.201600284
20. Singh N, Tiwari S, Srivastava KK, Siddiqi MI (2015) Identification of novel inhibitors of
Mycobacterium tuberculosis PknG using pharmacophore based virtual screening, docking,
molecular dynamics simulation, and their biological evaluation. J Chem Inf Model
55:1120–1129. https://doi.org/10.1021/acs.jcim.5b00150
21. Wang Y, Dai Y, Wu X, Li F, Liu B, Li C, Liu Q, Zhou Y, Wang B, Zhu M, Cui R, Tan X,
Xiong Z, Liu J, Tan M, Xu Y, Geng M, Jiang H, Liu H, Ai J, Zheng M (2019) Discovery and
development of a series of Pyrazolo[3,4-d]pyridazinone compounds as the novel covalent
fibroblast growth factor receptor inhibitors by the rational drug design. J Med Chem
62:7473–7488. https://doi.org/10.1021/acs.jmedchem.9b00510
22. Xu M, Yu L, Wan B, Yu L, Huang Q (2011) Predicting inactive conformations of protein
kinases using active structures: conformational selection of type-II inhibitors. PLoS One 6:
e22644. https://doi.org/10.1371/journal.pone.0022644
23. Modi V, Dunbrack RL (2019) Defining a new nomenclature for the structures of active and
inactive kinases. Proc Natl Acad Sci U S A 116:6818–6827. https://doi.org/10.1073/pnas.
1814279116
24. Bethke E, Pinchuk B, Renn C, Witt L, Schlosser J, Peifer C (2016) From type I to type II:
design, synthesis, and characterization of potent pyrazin-2-ones as DFG-out inhibitors of
PDGFRβ. ChemMedChem 11:2664–2674. https://doi.org/10.1002/cmdc.201600494
25. Zhao H, Caflisch A (2013) Discovery of ZAP70 inhibitors by high-throughput docking into a
conformation of its kinase domain generated by molecular dynamics. Bioorg Med Chem Lett
23:5721–5726. https://doi.org/10.1016/j.bmcl.2013.08.009
26. Pedreira JGB, Nahidino P, Kudolo M, Pantsar T, Berger B-T, Forster M, Knapp S, Laufer S,
Barreiro EJ (2020) Bioisosteric replacement of arylamide-linked spine residues with
N-Acylhydrazones and selenophenes as a design strategy to novel dibenzosuberone derivatives
as type I 1/2 p38α MAP kinase inhibitors. J Med Chem 63(13):7347–7354. https://doi.org/10.
1021/acs.jmedchem.0c00508
27. Henzler-Wildman K, Kern D (2007) Dynamic personalities of proteins. Nature 450:964–972.
https://doi.org/10.1038/nature06522
38
A. Poso