Testing amino acid-codon affinity hypothesis using molecular docking

Genetic code refers to a set of rules that assign trinucleotides called codons to amino acids in the process of protein synthesis. Investigating the genetic code's logic and its evolutionary origin has always been both intriguing and challenging. While the correspondence rules between codons and amino acids in the genetic code are well-known, it is still unclear whether those assignments can be explained based on energetic or/and entropic arguments. As an attempt at deciphering basic thermodynamic rules governing DNA translation, we used molecular docking to investigate the ability of amino acids to bind to their corresponding anticodon compared to other codons. The total number of 1280 direct docking interactions have been performed for each amino acid-codon/anti-codon case to find whether the amino acids have a preference to bind to their cognate anticodons or codons. Based on docking scores which are expected to correlate with binding affinity, no correlation with genetic correspondence rules was observed suggesting a more subtle process, other than direct binding, to explain codon-amino-acid specificity.