6HHR

Hsp90 in complex with 5-(2,4-Dihydroxy-phenyl)-4-(2-fluoro-phenyl)-2,4-dihydro-[1,2,4]triazole-3-thione

6HHR の概要

• エントリーDOI: 10.2210/pdb6hhr/pdb
• 分子名称: Heat shock protein HSP 90-alpha, 3-[2,4-bis(oxidanyl)phenyl]-4-(2-fluorophenyl)-1~{H}-1,2,4-triazole-5-thione, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: chaperone, atp binding
• 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: 23662.78

構造登録者

Musil, D.,Lehman, M.,Eggenweiler, H.-M. (登録日: 2018-08-29, 公開日: 2019-07-10, 最終更新日: 2024-05-15)

主引用文献

Schuetz, D.A.,Bernetti, M.,Bertazzo, M.,Musil, D.,Eggenweiler, H.M.,Recanatini, M.,Masetti, M.,Ecker, G.F.,Cavalli, A.
Predicting Residence Time and Drug Unbinding Pathway through Scaled Molecular Dynamics.
J.Chem.Inf.Model., 59:535-549, 2019

PubMed Abstract: Computational approaches currently assist medicinal chemistry through the entire drug discovery pipeline. However, while several computational tools and strategies are available to predict binding affinity, predicting the drug-target binding kinetics is still a matter of ongoing research. Here, we challenge scaled molecular dynamics simulations to assess the off-rates for a series of structurally diverse inhibitors of the heat shock protein 90 (Hsp90) covering 3 orders of magnitude in their experimental residence times. The derived computational predictions are in overall good agreement with experimental data. Aside from the estimation of exit times, unbinding pathways were assessed through dimensionality reduction techniques. The data analysis framework proposed in this work could lead to better understanding of the mechanistic aspects related to the observed kinetic behavior.

PubMed: 30500211
DOI: 10.1021/acs.jcim.8b00614

実験手法

X-RAY DIFFRACTION (2 Å)