Quantum Tunneling of the Methyl Group During DNA Histone Methylation: a Quantum Computational Model

Histone methylation is one of the molecular mechanisms of epigenetics in which a methyl group or more can be added to the DNA histone proteins. Histone methylation can alter gene expression and thus the overall cellular function. The transfer of the methyl group from the donor AdoMet to the lysine residue of the histone can be mediated via classical transfer or quantum tunneling. In the present study, we aim to explore the role of quantum tunneling in histone methylation compared with the classical transfer of methyl groups. Our results indicate that quantum tunneling provides a wide range of lifetimes for methylated histones between 1.56 x 10-13 s and 1.97 x 10118 s according to the energy of the methyl group and the number of transferred methyl groups. In addition, the tunneling delay time of the methyl group is within a fraction of a picosecond, which is a reasonable time and consistent with the time required for molecular transitions. Our results showed that quantum tunneling favors hypo-methylated histones because the ratio between the lifetimes of the reversed and forward reactions τ_(Q_r )/τ_(Q_f ) equals 1, while classical transfer favors hyper-methylated histones because the same ratio for the classical transfer τ_(C_r )/τ_(C_f ) can range from 4.73 x 108 to 9.6 x 104, depending on the number of transferred methyl groups. However, the ratio is between (1- 4.73 x 108) when either the classical or the quantum transfer is dominant during either the forward or reversed reactions. Moreover, temperature and enzymatic dynamics are important factors that can modulate the lifetime of methylation states.