Chirality in a quaternionic representation of the genetic code

A quaternionic representation of the genetic code, previously reported by the authors, is updated in order to incorporate chirality of nucleotide bases and amino acids. The original representation assigns to each nucleotide base a prime integer quaternion of norm 7 and involves a function that associates with each codon, represented by three of these quaternions, another integer quaternion (amino acid type quaternion) in such a way that the essentials of the standard genetic code (particulaty its degeneration) are preserved. To show the advantages of such a quaternionic representation we have, in turn, associated with each amino acid of a given protein, besides of the type quaternion, another real one according to its order along the protein (order quaternion) and have designed an algorithm to go from the primary to the tertiary structure of the protein by using type and order quaternions. In this context, we incorporate chirality in our representation by observing that the set of eight integer quaternions of norm 7 can be partitioned into a pair of subsets of cardinality four each with their elements mutually conjugates and by putting they in correspondence one to one with the two sets of enantiomers (D and L) of the four nucleotide bases adenine, cytosine, guanine and uracil, respectively. Thus, guided by two diagrams proposed for the codes evolution, we define functions that in each case assign a L- (D-) amino acid type integer quaternion to the triplets of D- (L-) bases. The assignation is such that for a given D-amino acid, the associated integer quaternion is the conjugate of that one corresponding to the enantiomer L. The chiral type quaternions obtained for the amino acids are used, together with a common set of order quaternions, to describe the folding of the two classes, L and D, of homochiral proteins.Comment: 17 pages, 9 figures. arXiv admin note: substantial text overlap with arXiv:1505.0465

Biophysical Interactions Underpin the Emergence of Information in the Genetic Code

The genetic code conceals a ‘code within the codons’, which hints at biophysical interactions between amino acids and their cognate nucleotides. Yet, research over decades has failed to corroborate systematic biophysical interactions across the code. Using molecular dynamics simulations and NMR, we have analysed interactions between the 20 standard proteinogenic amino acids and 4 RNA mononucleotides in 3 charge states. Our simulations show that 50% of amino acids bind best with their anticodonic middle base in the −1 charge state common to the backbone of RNA, while 95% of amino acids interact most strongly with at least 1 of their codonic or anticodonic bases. Preference for the cognate anticodonic middle base was greater than 99% of randomised assignments. We verify a selection of our results using NMR, and highlight challenges with both techniques for interrogating large numbers of weak interactions. Finally, we extend our simulations to a range of amino acids and dinucleotides, and corroborate similar preferences for cognate nucleotides. Despite some discrepancies between the predicted patterns and those observed in biology, the existence of weak stereochemical interactions means that random RNA sequences could template non-random peptides. This offers a compelling explanation for the emergence of genetic information in biology

Antisense Peptide Technology for Diagnostic Tests and Bioengineering Research

Antisense peptide technology (APT) is based on a useful heuristic algorithm for rational peptide design. It was deduced from empirical observations that peptides consisting of complementary (sense and antisense) amino acids interact with higher probability and affinity than the randomly selected ones. This phenomenon is closely related to the structure of the standard genetic code table, and at the same time, is unrelated to the direction of its codon sequence translation. The concept of complementary peptide interaction is discussed, and its possible applications to diagnostic tests and bioengineering research are summarized. Problems and difficulties that may arise using APT are discussed, and possible solutions are proposed. The methodology was tested on the example of SARS-CoV-2. It is shown that the CABS-dock server accurately predicts the binding of antisense peptides to the SARS-CoV-2 receptor binding domain without requiring predefinition of the binding site. It is concluded that the benefits of APT outweigh the costs of random peptide screening and could lead to considerable savings in time and resources, especially if combined with other computational and immunochemical methods

The evolution of the genetic code: Impasses and challenges

The origin of the genetic code and translation is a “notoriously difficult problem”. In this survey we present a list of questions that a full theory of the genetic code needs to answer. We assess the leading hypotheses according to these criteria. The stereochemical, the coding coenzyme handle, the coevolution, the four-column theory, the error minimization and the frozen accident hypotheses are discussed. The integration of these hypotheses can account for the origin of the genetic code. But experiments are badly needed. Thus we suggest a host of experiments that could (in)validate some of the models. We focus especially on the coding coenzyme handle hypothesis (CCH). The CCH suggests that amino acids attached to RNA handles enhanced catalytic activities of ribozymes. Alternatively, amino acids without handles or with a handle consisting of a single adenine, like in contemporary coenzymes could have been employed. All three scenarios can be tested in in vitro compartmentalized systems

Experimental Test of L- and D-Amino Acid Binding to L- and D-Codons Suggests that Homochirality and Codon Directionality Emerged with the Genetic Code

L-amino acids bind preferentially to their D-codons, but almost nothing is known about whether D-amino acids correspondingly prefer L-codons, or how codon directionality affects amino acid binding. To investigate these issues, two D-RNA-oligonucleotides having inverse base sequences (D-CGUA and D-AUGC) and their corresponding L-RNA-oligonucleotides (L-CGUA and L-AUGC) were synthesized and their affinity determined for Gly and eleven pairs of L- and D-amino acids. The data support the hypothesis (Root-Bernstein, Bioessays 2007; 29: 689–698) that homochirality and codon directionality emerged as a function of the origin of the genetic code itself. Further tests involving amplification methods are proposed