Synthesis of RNA nucleotides in plausible prebiotic conditions from ab initio computer simulations

Understanding the mechanism of spontaneous formation of ribonucleotides under realistic prebiotic conditions is a key open issue of origins-of-life research. In cells, <i>de novo</i> and salvage nucleotide enzymatic synthesis combines 5-phospho-α -D-ribose-1-diphosphate ( α-PRPP) and nucleobases. Interestingly, these reactants are also known as prebiotically plausible compounds. Combining ab initio molecular dynamics simulations with recently developed reaction exploration and enhanced sampling methods, we show that nucleobases and α -PRPP should spontaneously combine, under mild hydrothermal conditions, with an exothermic reaction and a facile mechanism, forming both purine and pyrimidine ribonucleotides.<br>Surprisingly, this mechanism is very similar to the biological one, and yields ribonucleotides with the same anomeric carbon chirality as in biological systems.<br>These results suggest that natural selection might have optimized -- through enzymes -- a pre-existing ribonucleotide formation mechanism, carrying it forward to modern life forms.<br>