Biomedical subjects

G Raghunathan

Publications and source records attributed to G Raghunathan.

23 records · Page 2Linked to original sources

PubMed1987

Structural elements and organization of the ancestral translational machinery.

The molecular mechanisms underlying the primitive translational apparatus have been studied in light of present day protein biosynthesis. Using the structural information available from the contemporary system as a key to its function, both the structural necessities for an early adaptor and the multipoint recognition properties of such adaptors have been investigated. This was done by first critically examining the potential feasibility of right- and left-handed hairpin adaptor models. Second, a molecular model of the contemporary transpeptidation complex has been constructed in order to ascertain the structural requirements of the adaptor molecule needed for peptidyl transfer. Third, a model of the tRNATyr-tyrosyl tRNA synthetase complex including the positioning of the disordered region is proposed. This model is used to illustrate those required recognition properties of aminoacyl synthetase which lead to a perspective on the structure of the ancestor synthetase.

Amino Acyl-tRNA Synthetases↗

PubMed1987

Structural requirements for a primitive adaptor molecule.

Adaptor properties of linear hairpin helices have been examined. The analysis suggests that neither right nor left handed hairpin helices can simultaneously read a comma free messenger and align aminoacyl residues for peptide condensation. Comparison of these studies with the model of the present day peptidyl transfer intermediate suggests that the "L" shaped folding of the present day tRNAs may be a prerequisite for adaptor function. Therefore, the three-dimensional organization of the ancestral adaptor molecule must have had structural features similar to its present day counterpart.

Amino Acids↗

PubMed1986

Multistep modeling (MSM) of biomolecular structure application to the A-G mispair in the B-DNA environment.

A multistep modeling procedure has been evolved to study the structural changes introduced by lesions in DNA. We report here the change in the structure of regular B-DNA geometry due to the incorporation of Ganti-Aanti mispair in place of a regular G-C pair, preserving the helix continuity. The energetics of the structure so obtained is compared with the Ganti-Asyn configuration under similar constrained conditions. We present the methodology adopted and discuss the results.

Computer Graphics↗

PubMed1985

Conformational relationships between amino acids and their anticodons in the primitive decoding system.

Detailed calculations of the conformational characteristics of a primitive decoding system are presented. A penta-nucleotide serves as the primitive tRNA (PIT) with a triplet of primitive anticodon (PAC) in a helical conformation. This molecular moiety has a cleft in the middle. An amino acid can comfortably nestle into the cleft. The conformation of this molecular association is stabilised by a few hydrogen bonds. The stereochemistry of the moiety restricts the conformational possibilities and the sidechain of the amino acid gets oriented at a proper position and in the correct direction to interact intimately with the PAC in the middle of the PIT. The model favours L-amino acids for beta-D-ribonucleotides. The location of the sidechain of the amino acid in the PIT gives a raison d'être for the important features of the organisation of nucleotide triplets for amino acids in the Genetic Code. The interaction of a few key amino acids with the different combinations of bases as PAC sequences has been studied and the stereochemical basis for the selection of the anticodons for amino acids is elucidated.

Amino Acids↗

PubMed1980

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.

Animals↗