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It is important to mention that MD simulation under implicit solvent model has been marked as less reliable and detected with dissociation of ligand from the binding site in the receptor 106

Several factors influence DPP-4 activity: Genetics: Polymorphisms in the DPP4 gene affect enzyme expression and activity Metabolic status: Insulin resistance correlates with elevated DPP-4 activity Inflammation: Chronic inflammation increases DPP-4 expression Age: DPP-4 activity tends to increase with aging Diet composition: Certain dietary patterns modulate DPP-4 expression This variability explains why some people maintain better natural GLP-1 levels than others, even with similar L-cell activation strategies

acknowledges the support of an Emmy Noether Award from the German Research Foundation (DFG, 467788900) and the Ministry of Culture and Science of the State of North Rhine-Westphalia (NRW-Nachwuchsgruppenprogramm)

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