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Research Articles

Mss51 protein inhibition serves as a novel target for type 2 diabetes: a molecular docking and simulation study

ORCID Icon, ORCID Icon, , , &
Pages 4862-4869 | Received 27 Mar 2023, Accepted 05 Jun 2023, Published online: 20 Jun 2023
 

Abstract

Myostatin is a widely recognized inhibitory factor of skeletal muscle growth and significantly influences muscle development and metabolism. In mice, myostatin inhibition improves insulin sensitivity, increases glucose uptake by skeletal muscle, and reduces body fat. Furthermore, Mss51 is downregulated in response to myostatin inhibition, and its deletion appears to improve the metabolic state of skeletal muscle and reduce adipose tissue, which makes Mss51 a potential target for the treatment of obesity and type 2 diabetes. Here, we report a computationally predicted and validated three-dimensional structure of Mss51. Computational screening was used to identify naturally occurring compounds from the Herbal and Specs chemical database that might inhibit Mss51, based on binding affinities and physiochemical and ADMET properties. ZINC00338371, ZINC95099599 and ZINC08214878 were found to bind to Mss51 with high binding affinity and specificity. In addition, 100 ns molecular dynamics simulations were conducted to assess the stabilities of the interactions between the three compounds and Mss51. MD simulation demonstrated that all three compounds bind to the active pocket site of Mss51 stably and cause conformation changes. ZINC00338371 was found to bind most stably with binding free energy −229.022 ± 13.776 kJ/mol to Mss51, suggesting that it has therapeutic potential as a treatment option for obesity and type 2 diabetes.

Communicated by Ramaswamy H. Sarma

Disclosure statement

The authors declare that they have no conflict of interest.

Data availability

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

Funding

This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education [2020R1A6A1A03044512]. In addition, the study was supported by the Forestry (IPET) through High Value-added Food Technology Development Program of the Korea Institute of Planning and Evaluation for Technology in Food and Agriculture funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA) [322008-5].

Additional information

Funding

This research was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education [2020R1A6A1A03044512]. In addition, the study was supported by the Forestry (IPET) through High Value-added Food Technology Development Program of the Korea Institute of Planning and Evaluation for Technology in Food and Agriculture funded by the Ministry of Agriculture, Food, and Rural Affairs (MAFRA) [322008-5].

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