Citation: Zhang Ling, Liu Yingxiang, Zhao Zhongxiang, Cai Xiaoli, Ma Yuzhuo. Study on the Interation of Indazole Derivatives with PI3Kδ Inhibitors by 3D-QSAR, Docking and Molecular Dynamics Simulation[J]. Chemistry, ;2018, 81(2): 148-157. shu

Study on the Interation of Indazole Derivatives with PI3Kδ Inhibitors by 3D-QSAR, Docking and Molecular Dynamics Simulation

1.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006
2.
College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006

Corresponding author: Liu Yingxiang, liuyingxiang62@162.com
Received Date: 29 September 2017
Accepted Date: 5 December 2017

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Phosphoinositide 3-kinase delta (PI3Kδ) is involved in inflammatory process of chronic obstructive pulmonary disease (COPD) and has been identified as a new potential therapeutic target. In this paper, three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics were used to study the interaction between 47 indazole derivatives and P13Kδ, and corresponding models were established. The comparative molecular field analysis (CoMFA) model q²=0.719, r²=0.972, comparative molecular similarity index analysis (CoMSIA) model q²=0.649, r²=0.983, indicating that constructed QSAR models have stable and reliable predictive ability. CoMFA and CoMSIA contour maps could graphically describe the effect of different fields on activity. The steric, hydrophobic and hydrogen bond acceptor fields have greater contribution to the activity. Then, the binding mode of small molecule and P13Kδ was explored by molecular docking. The results showed that indazole compounds were mainly bound to P13Kδ by hydrogen bonding and hydrophobic interaction, and the results of docking were further verified by molecular dynamics simulation. Finally, eight compounds were designed based on the information obtained from the contour maps, docking mode and molecular dynamics simulation, they can combine well with PI3Kδ.
- PI3Kδ,
- Molecular docking,
- 3D-QSAR,
- Molecular dynamics simulation
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沈阳化工大学材料科学与工程学院沈阳 110142