Molecular Dynamics Simulations Reveal Heavy Water-Induced Structural Changes in Subunit c of ATP Synthase and Formation of Aligned Clusters.

aims: In this study, we aimed to analyze the effect of D2O on the structure of ATP synthase’s c subunit. background: Deuterium is a stable isotope of hydrogen with an abundance of ~1/6600. Since water contains 2 hydrogens, the abundance of deuterated water (heavy water [D2O] + semiheavy water [HDO]) is ~1/3300. This corresponds to ~15 mM concentration in human plasma that is several times higher than several common electrolytes. Despite this very high concentration, its effects on human health and aging are generally neglected. Deuterated water can generate deuteron through spontaneous ionization. The exchange of deuteron with ionizable hydrogen in other molecules is called deuteronation and is a common stochastic process that changes the structure and function of proteins and other macromolecules. objective: Our objective was to analyze the effect of different concentrations of D2O on the structure of ATP synthase’s c subunit. method: We made our analyses by using molecular dynamics (MD) simulations. result: D2O changed the structure of the c subunit starting from a concentration that is lower than half of its natural abundance. At high concentrations, D2O started to behave strangely by forming aligned and clustered structures. conclusion: Our results can be useful in the elucidation of the mechanisms of deuterium-depleted water’s (DDW, light water) published health benefits. Our study shows the importance of analysis of structural changes that occur in all macromolecules over a range of D2O concentrations that have biological relevance. other: At least this structural change observed in the ATP synthase's c subunit could have broader implications for biological processes or health.