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PT-2 step of Mechanism 1 in EGFR has a higher barrier but is less exergonic compared to that in solution We next performed the one-dimensional free energy simulations to investigate proton transfer (PT-2) from the -DMAM nitrogen to the C atom of afatinib in both EGFR and solution (Figure 2e and f)

This pump failure triggers a depolarization wave that radiates outward from the site of origin

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