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Fig. 6 | Journal of Cheminformatics

Fig. 6

From: Data driven polypharmacological drug design for lung cancer: analyses for targeting ALK, MET, and EGFR

Fig. 6

Structural variabilities and activation states of the targets. a A cartoon style plot showing the activation loops of representative crystal structures for MET (green PDBIDs 1R0P, 3DKC, 3F66, 3L8V, 3Q6W and 3RHK) and ALK (red both monomers from PDBID 4CNH) shows the diversity of positions for the tyrosine side chain suitable for crizotinib pi-stacking interactions (MET: Tyr1230, aligned position in ALK: Tyr1278). The ALK structures are two monomers from a single PDB structure that show different activation loop geometries. b Different shapes of the ATP binding sites arise from activation loop structural differences, among other differences. Here, structures for crizotinib-ALK (red PDBID: 2YFX), a pyrido-pyrimidine inhibitor and MET (violet PDBID: 4GG7), and ARQ197-MET (turquoise PDBID: 3RHK) are superimposed. c Distributions of activation relevant geometries for PDB structures of ALK, MET, and EGFR. The axes represent the first two dimensions of a PLS analysis to identify the geometric parameters most relevant to identify active and inactive states (see text)

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