Specific Protein-Nucleic Acid Base Interactions in a Simple Prebiotic Genetic Code

Powerful computer facilities and the features of Gaussian98 will be used to unravel the nature of specific protein-nucleic acid base interactions which led to a simple prebiotic genetic code, which has so far not become apparent from model-building experiments. This work seeks to provide the vital key to the structural relationships between amino-acids and their codons. The origin of the genetic code is still an unexplored area of chemistry whose understanding should lead to the development of molecules able to interact with specific genes. These extensive calculations are perhaps best best done with the objectivity provided by ab initio methods and the high-performance computer facilities uniquely available through the APAC National Facility.

Principal Investigator

Neville Bofinger
Natural Resource Sci.
Queensland University of Technology

Project

e98

Co-Investigators

Nigel Aylward
Physical Sciences
Queensland University of Technology

RFCD Codes

250699

Significant Achievements, Anticipated Outcomes and Future Work

Origins of the Genetic Code in Prebiotic Molecular Evolution on Earth
(poster abstract, Fifth European Symposium of The Protein Society. Florence, Italy, March 29 - April 2, 2003)
Polymerisation of cyclic nucleoside 3’-5’ phosphoacyl amino-acids is postulated to be the origin of RNA and associated protein in prebiotic molecular evolution. The enthalpy change in the intramolecular interaction between the nucleoside base and the amino-acid side chain determines the stability of the particular complex, resulting in a preferred association (or coding) of a base for a particular amino-acid. The compounds studied were guanosine 3’-5’ phosphoacyl glycine where the strong hydrogen bond between protonated glycine and guanine N7 gives an enthalpy change of -0.05 h. Similarly, hydrogen bonds in cyclic adenosine 3’-5’ phosphoacyl L-lysine give an enthalpy change of -0.04 h. Hydrophobic interactions in uridine 3’-5’ phosphoacyl L-phenylalanine give an enthalpy change of -0.02 h and the corresponding value for cyclic cytidine 3’-5’ phosphoacyl L-proline is -0.01 h. These interactions were expected to be modified as the genetic code became a duplet and finally a triplet code. The interactions have been shown to be feasible from the overall enthalpy changes in the ZKE approximation at the MP2 /6-31G* level.

N.N. Aylward, Jr., N. Bofinger, Sr. Origins of the Genetic Code in Prebiotic Molecular Evolution on Earth, Protein Science, Fifth European Symposium of The Protein Society, Program & Abstracts, Vol.12, Suppl.1, 2003, 171. Cold Spring Harbor Laboratory Press.

Four papers have been written on each of the nucleic-acid base - amino-acid codings and submitted as part of a thesis entitled, " The Structure and Electronic Properties of Molecular Clusters", presently under faculty review at Queensland University of Technology. It is expected that this work submitted in November 2003 will be published as a thesis during 2004. The papers incorporating the data mentioned above are also expected to be submitted to the journal, "Origin of Life and Evolution of the Biosphere", when review is complete.

This project is now suspended pending a more quantitative understanding of the stability of nucleic-acid base sequences, f96.

 

Computational Techniques Used

Gaussian98 ab initio geometry optimizations of amino-acid -nucleic acid base and template at the hf and mp2 levels, zero-point energy and electric potential. Approximately 50 - 60 atoms are mandatory. Gaussian98 is able to manage this calculation in an acceptable time frame at the MP2 level without a problem. There may be a referee request to compare the interaction energies in an aqueous environment which would require more computing facilities. The strength of the amino-acid -nucleic acid base interaction energies compared to the intrinsic nucleic acid base interaction energies should become apparent.

 

Publications, Awards and External Funding

External Funding and Awards

None.

Publications

N.N. Aylward, Jr., N. Bofinger, Sr. Origins of the Genetic Code in Prebiotic Molecular Evolution on Earth, Protein Science, Fifth European Symposium of The Protein Society, Program & Abstracts, Vol.12, Suppl.1, 2003, 171. Cold Spring Harbor Laboratory Press.

N.N.Aylward, Thesis, "The Structure and Electronic Properties of Molecular Clusters", 2003, 1-500. In press