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With the Modigy [28] workflow, a total of 564 amino acid sequences were computationally designed with three missense mutations according to the sequence template of semaglutide backbone in Figure 1, where Modeller [29] was used to generate at least 5000 homology complex structural models of GLP-1R ECD-semaglutide analogue with PDB entry 4ZGM [24, 35] as the structural template, and afterwards, for each structural model, Prodigy [30, 31] was used for the structural biophysics-based calculations of K d between semaglutide analogues and GLP-1R ECD

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