6BIK

BTK complex with compound 7

6BIK の概要

• エントリーDOI: 10.2210/pdb6bik/pdb
• 関連するPDBエントリー: 6AUA 6AUB 6BKE 6BKH 6BKW 6BLN 6EP9
• 分子名称: 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)
• 機能のキーワード: btk, inhibitor, water structure, kinase, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34855.68

構造登録者

Kiefer, J.R.,Eigenbrot, C.,Yu, C.L. (登録日: 2017-11-02, 公開日: 2018-11-07, 最終更新日: 2019-03-27)

主引用文献

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

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: 30756207
DOI: 10.1007/s10822-019-00187-y

実験手法

X-RAY DIFFRACTION (1.901 Å)