Molecular dynamics simulation and steered molecular dynamics simulation on irisin dimers
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Irisin is found closely associated with promoting the browning of beige fat cells in white adipose tissue. The crystal structure reveals that irisin forms a continuous inter-subunit β-sheet dimer. Here, molecular dynamics (MD) simulation and steered molecular dynamics (SMD) simulation were performed to investigate the dissociation process and the intricate interactions between the two irisin monomers. In the process of MD, the interactions between the monomers were roughly analyzed through the average numbers of both hydrophobic contacts and H-bonds. Then, SMD was performed to investigate the accurate interaction energy between the monomers. By the analysis of dissociation energy, the van der Waals (vdW) force was identified as the major energy to maintain the dimer structure, which also verified the results of MD simulation. Meanwhile, 11 essential residues were discovered by the magnitude of rupture force during dissociation. Among them, residues Arg75, Glu79, Ile77, Ala88, and Trp90 were reported in a previous study using the method of mutagenesis and size exclusion chromatography, and several new important residues (Arg72, Leu74, Phe76, Gln78, Val80, and Asp91) were also identified. Interestingly, the new important residues that we discovered and the important residues that were reported are located in the opposite side of the β-sheet of the dimer.
KeywordsMolecular dynamics simulation Steered molecular dynamics simulation Irisin dimer Protein–protein interactions
This work was supported by the National Natural Science Foundation of China (31570154 and 31201285); the China Postdoctoral Science Foundation (2017 M611752), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry of China (2013693); the Serving Local Project of the Education Department of Liaoning Province, China (LFW201704) and the Science and Technology Support Program from Shenyang City (17136800).
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