tyThe raw clinical, malaria outcomes, and pharmacokinetic information made use of in this study have been deposited in databases available at doi.org/10.5281/zenodo.5602139. The information generated within this study for the figures that use model-generated information are offered inside the Source Data file. Supply data are supplied with this paper.Code availabilityThe code employed for these analyses is readily available at doi.org/10.5281/zenodo.5562807.Received: 24 March 2021; Accepted: 29 October 2021;
moleculesArticleComputational Identification of Dithymoquinone as a Prospective Inhibitor of Myostatin and Regulator of Muscle MassSyed Sayeed Ahmad 1,two , Khurshid Ahmad 1,two , Eun Ju Lee 1,2 , Sibhghatulla Shaikh 1,and Inho Choi 1,2, Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea; sayeedahmad4@gmail (S.S.A.); ahmadkhursheed2008@gmail (K.A.); [email protected] (E.J.L.); sibhghat.88@gmail (S.S.) Analysis Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Korea Correspondence: [email protected]; Fax: +82-Citation: Ahmad, S.S.; Ahmad, K.; Lee, E.J.; Shaikh, S.; Choi, I. Computational Identification of Dithymoquinone as a Prospective Inhibitor of Myostatin and Regulator of Muscle Mass. Molecules 2021, 26, 5407. doi.org/10.3390/ molecules26175407 Academic Editor: Angelo Facchiano Received: 19 August 2021 Accepted: 2 September 2021 Published: six SeptemberAbstract: The skeletal muscle (SM) could be the largest organ inside the Caspase 2 Inhibitor list physique and has tremendous regenerative energy as a result of its myogenic stem cell population. Myostatin (MSTN), a protein created by SM, is released in to the bloodstream and is responsible for age-related reduced muscle fiber improvement. The objective of this study was to identify the organic compounds that inhibit MSTN with therapeutic potential for the management of age-related problems, specifically muscle atrophy and sarcopenia. Sequential screening of 2000 all-natural compounds was performed, and dithymoquinone (DTQ) was located to inhibit MSTN using a binding free power of -7.40 kcal/mol. Furthermore, the docking benefits showed that DTQ reduced the binding interaction in between MSTN and its receptor, activin receptor type-2B (ActR2B). The JAK1 Inhibitor list global energy of MSTN-ActR2B was identified to become reduced from -47.75 to -40.45 by DTQ. The stability of the DTQ STN complex was subjected to a molecular dynamics evaluation for as much as 100 ns to check the stability of your complex making use of RMSD, RMSF, Rg, SASA, and Hbond quantity. The complex was located to become steady just after ten ns for the finish of your simulation. These outcomes recommend that DTQ blocks MSTN signaling by way of ActR2B and that it has potential use as a muscle growth-promoting agent through the aging course of action. Search phrases: myostatin; dithymoquinone; natural compounds; molecular dynamics; ActR2B; proteinprotein interaction1. Introduction Human skeletal muscle (SM) is often a extremely plastic tissue that accounts for up to 40 of total body weight and 505 of physique protein [1]. SM will be the biggest physique organ and is mainly responsible for movement, temperature handle, and keeping glucose levels mainly because muscle contraction utilizes glucose as a fuel supply [2]. Furthermore, SM has considerable regenerative possible in response to harm or disease on account of its myogenic stem cell population [3]. The maintenance of SM mass is dependent upon the balance involving protein synthesis and degradation, which are hugely sensitive to hormonal balance, nutritional status, exercising, injury, and illness [4]. Loss of SM mass is a marker of severa