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However, under conditions of oxidative stress and substrate/cofactor (like tetrahydrobiopterin, BH4) depletion during ischemia/reperfusion, eNOS can become uncoupled. In this state, it produces O 2 instead of NO

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Bonds involving hydrogen atoms were restrained using LINear Constraint Solver (LINCS) 23 to allow a 2 fs time-step

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