A conformational rationale for the origin of the mechanism of nucleicacid-directed protein synthesis of 'living' organisms.

The physical basis for the natural evolution of a primitive decoding system is presented using the concepts of molecular interactions. Oligoribonucleotides of five residues having U at the 5'-end, a purine at the 3'-end and any combination of three bases in the middle is taken as a primitive tRNA (PIT). From conformational considerations PIT is expected to have U-turn conformation wherein, N3-H3 of base U hydrogen-bonds with phosphate, three residues ahead leaving triplet bases called primitive anticodons (PAC) into a helical conformation, and this creates a cleft between U and PAC. An amino acid can be comfortably nestled into the cleft with the amide hydrogens and carboxyl oxygen hydrogen-bonded to the last purine and the first uridine, while the side-chain can interact with the cleft side of PAC. The other side of PAC is free to base-pair with triplet codons on a longer RNA. Also two PACs can 'recognize' consecutive triplet codons, and this leads to a dynamic interaction in which the amino and carboxyl ends are brought into proximity, making the formation of peptide bond feasible. The cleft formed by different anticodon triplets, broadly speaking, shows preferences for the corresponding amino acids of the presently known codon assignment. Thus the nucleicacid-directed protein synthesis, which is a unique feature of all 'living' organisms is shown to be a natural consequence of a particular way of favourable interaction between nucleic acids and amino acids, and our model provides the missing link between the chemical evolution of small organic molecules and biological evolution through the process of mutations in nucleicacids and nucleicacid-directed protein synthesis.