Potential energy calculations on conformations of puromycin and 3'-terminal aminoacyl adenosines of transfer RNAs

Abstract

Potential energy calculations taking into account van der Waals, electrostatic and torsional interactions have been carried out on puromycin, an inhibitor of protein synthesis, resembling the terminal 3'-aminoacyl adenosine moieties of charged transfer RNAs and comprising of an adenosine and an amino acid residue of tyrosine. The results reveal that the number of energetically favorable conformations for puromycin are strikingly limited and that the flexibility in the purpomycin molecule resides mainly in the rotation about the C^α -C^β bond of the amino acid residue while the favored rotational angles about the other bonds fall into their respective single domains. Three possible conformations which correspond to the three staggered orientations about the C^α -C^β bond, viz. 60°, 180° and 300° have been predicted for puromycin. These results have been found to be in excellent agreement with the X-ray data on puromycin and carbocyclic puromycin. The salient conformational features obtained for the amino acid portion in puromycin are very similar to those found in free amino acids and amino acid residues in proteins indicating that the nucleoside portion has virtually no significant influence on the preferred conformations of the amino acid moiety. It is likely that all the 20 different 3'-terminal aminoacyl adenosine moieties of charged transfer RNAs would exhibit conformational features very similar to that of puromycin with the amino acid portions displaying conformations characteristic of their own.