Theoretical study on the design of allosteric inhibitors of diabetes associated protein PTP1B

被引:0
|
作者
Zhan, Jiuyu [1 ]
Liu, Zhenyang [1 ]
Gao, Hongwei [1 ]
机构
[1] Ludong Univ, Sch Life Sci, Yantai, Shandong, Peoples R China
关键词
protein tyrosine phosphatase 1B; inhibitor; MD simulations; rational design; LUDI; MOLECULAR-DYNAMICS SIMULATION; PHOSPHATASE 1B INHIBITORS; BINDING; MECHANISM; INSIGHTS; OBESITY; WEIGHT;
D O I
10.3389/fphar.2024.1423029
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The protein tyrosine phosphatase 1B (PTP1B) is a critical therapeutic target for type 2 diabetes mellitus (T2DM). Many PTP1B inhibitors have been reported, however, most of them lack high specificity and have adverse effects. Designing effective PTP1B inhibitors requires understanding the molecular mechanism of action between inhibitors and PTP1B. To this end, molecular dynamics (MD) simulations and molecular mechanics Poisson Boltzmann Surface Area (MM-PB/SA) methods were used to observe the binding patterns of compounds with similar pentacyclic triterpene parent ring structures but different inhibition abilities. Through structure and energy analysis, we found that the positions of cavities and substituents significantly affect combining capacity. Besides, we constructed a series of potential inhibitor molecules using LUDI and rational drug design methods. The ADMET module of Discovery Studio 2020 was used to predict the properties of these inhibitor molecules. Lastly, we obtained compounds with low toxicity and significant inhibitory activity. The study will contribute to the treatment of T2DM.
引用
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页数:16
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