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

• DOI: 10.3389/fphar.2024.1423029
• Publication Date: 2024-08-22T04:56:15Z
• Authors: Jiuyu Zhan; Zhenyang Liu; Hongwei Gao
• Keywords: Molecular mechanics; Rational design

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 adverse effects. Designing effective requires understanding the molecular mechanism action between PTP1B. To this end, dynamics (MD) simulations mechanics Poisson Boltzmann Surface Area (MM-PB/SA) methods were used to observe binding patterns compounds with similar pentacyclic triterpene parent ring structures but different inhibition abilities. Through structure energy analysis, we found that positions cavities substituents significantly affect combining capacity. Besides, constructed series potential inhibitor molecules using LUDI rational drug design methods. ADMET module Discovery Studio 2020 was predict properties these molecules. Lastly, obtained low toxicity significant inhibitory activity. study will contribute treatment T2DM.