9N4U

Crystal structure of PAK1 bound to compound R1

これはPDB形式変換不可エントリーです。

9N4U の概要

• エントリーDOI: 10.2210/pdb9n4u/pdb
• 分子名称: Glutathione S-transferase class-mu 26 kDa isozyme,Serine/threonine-protein kinase PAK 1, (3M)-3-[(4P)-2-chloro-4-(6-methylpyridin-2-yl)phenyl]-1-{2-[2-(dimethylamino)ethoxy]ethyl}-1,6-naphthyridin-2(1H)-one (3 entities in total)
• 機能のキーワード: kinase, inhibitor, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123594.93

構造登録者

Wang, W.,Oh, A.,Kiefer, J.R.,Hsu, P.L. (登録日: 2025-02-03, 公開日: 2025-06-25, 最終更新日: 2025-07-02)

主引用文献

Walters, B.T.,Patapoff, A.W.,Kiefer, J.R.,Wu, P.,Wang, W.
Integrating Hydrogen Exchange with Molecular Dynamics for Improved Ligand Binding Predictions.
J.Chem.Inf.Model., 65:6144-6154, 2025

PubMed Abstract: We introduce hydrogen-exchange experimental structure prediction (HX-ESP), a method that integrates hydrogen exchange (HX) data with molecular dynamics (MD) simulations to accurately predict ligand binding modes, even for targets requiring significant conformational changes. Benchmarking HX-ESP by fitting two ligands to PAK1 and four ligands to MAP4K1 (HPK1) and comparing the results to X-ray crystallography structures, demonstrates that HX-ESP can identify binding modes across a range of affinities significantly outperforming flexible docking for ligands necessitating large conformational adjustments. By objectively guiding simulations with experimental HX data, HX-ESP overcomes the long time scales required for binding predictions using traditional MD. This advancement enhances the accuracy of computational modeling in drug discovery and thus will accelerate the development of effective therapeutics.

PubMed: 40495786
DOI: 10.1021/acs.jcim.5c00397

実験手法

X-RAY DIFFRACTION (1.77 Å)