Nucleotide radicals in DNA/RNA synthesis. Computational approach
1University ofManchester,OxfordRoad,Manchester,M13 9PL, (UK)
2Saint-Petersburg StateUniversity,Universitetskaya Emb. 7/9, 199034, Saint-Petersburg, (RUSSIANFEDERATION)
A new radical mechanism of nucleotide polymerization is found. The finding is based on the Car-Parrinello molecular dynamics computations at 310 K with an additional spin-spin coupling term for 31P and 1H atoms and a radical pair spin term included. The mechanism is initiated by a creation of a high-energy spin-separated Mg-ATP complex in a triplet state in which theMg prefers an uncommon chelation to the O2-O3 oxygens of theATP. The cleavage of the complex produces the ! AMP- and ! O- radicals. The latter captures a proton from acidic solution (the Zundel cation) that converts it into the ! OH radical. The process agrees with the proton-coupled electron transfer (PCET) mechanism. Through interacting with the HO-C3' group of the deoxyribose/ribose the
! OH radical captures its hydrogen atom. The process is accompanied by producing water and the ! AMP radical. The ! AMP- andAMP radicals then interact yielding a dimer. The described mechanism is easily generalized for a bigger number of adjoining nucleotides and their type. The radical mechanism is highly sensitive to the ! AMP-" ! OH radical pair spin symmetry and the radius of the ! OH diffusion. This confines the operation of the radical mechanism: it is applicable to nucleotide polymerization through the HO-C3' group of deoxyribose/ribose (DNA/RNA polymerization) and inapplicable through the HO-C2' group of ribose (RNA) " a result that nature has developed over evolution.
Nucleotide radicals, DNA/RNA