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Accurate estimation of ligand binding affinity changes upon protein mutation

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Increased cAMP upregulates protein kinase A (PKA) and exchange protein activated by cAMP, which leads to rapid increases in intracellular calcium and insulin exocytosis in a glucose-dependent manner [33]

The mechanism is understood (renal D-amino acid oxidase metabolizes the proapoptotic domain), but understanding the mechanism does not eliminate the risk