6BIK
BTK complex with compound 7
Summary for 6BIK
| Entry DOI | 10.2210/pdb6bik/pdb |
| Related | 6AUA 6AUB 6BKE 6BKH 6BKW 6BLN 6EP9 |
| Descriptor | Tyrosine-protein kinase BTK, SULFATE ION, 4-tert-butyl-N-[2-(hydroxymethyl)-3-(1-methyl-5-{[5-(morpholine-4-carbonyl)pyridin-2-yl]amino}-6-oxo-1,6-dihydropyridazin-3-yl)phenyl]benzamide, ... (5 entities in total) |
| Functional Keywords | btk, inhibitor, water structure, kinase, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34855.68 |
| Authors | Kiefer, J.R.,Eigenbrot, C.,Yu, C.L. (deposition date: 2017-11-02, release date: 2018-11-07, Last modification date: 2019-03-27) |
| Primary citation | Nittinger, E.,Gibbons, P.,Eigenbrot, C.,Davies, D.R.,Maurer, B.,Yu, C.L.,Kiefer, J.R.,Kuglstatter, A.,Murray, J.,Ortwine, D.F.,Tang, Y.,Tsui, V. Water molecules in protein-ligand interfaces. Evaluation of software tools and SAR comparison. J. Comput. Aided Mol. Des., 33:307-330, 2019 Cited by PubMed Abstract: Targeting the interaction with or displacement of the 'right' water molecule can significantly increase inhibitor potency in structure-guided drug design. Multiple computational approaches exist to predict which waters should be targeted for displacement to achieve the largest gain in potency. However, the relative success of different methods remains underexplored. Here, we present a comparison of the ability of five water prediction programs (3D-RISM, SZMAP, WaterFLAP, WaterRank, and WaterMap) to predict crystallographic water locations, calculate their binding free energies, and to relate differences in these energies to observed changes in potency. The structural cohort included nine Bruton's Tyrosine Kinase (BTK) structures, and nine bromodomain structures. Each program accurately predicted the locations of most crystallographic water molecules. However, the predicted binding free energies correlated poorly with the observed changes in inhibitor potency when solvent atoms were displaced by chemical changes in closely related compounds. PubMed: 30756207DOI: 10.1007/s10822-019-00187-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.901 Å) |
Structure validation
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