Understanding the origins of life on Earth is one of the most intriguing problems facing science today. In the research presented here, we apply computational methods to explore origins of life scenarios. In particular, we focus on the origins of the genetic code and the intersection between geochemistry and a primordial ``biochemistry" in which mononucleotides could form short oligoucleotide chains. We also apply quantum chemical methods to a modern biochemical reaction, the charging of tRNA by an aminoacyl-tRNA synthetase, in order to shed light on the possible chemistry one may want to consider in problems relating to the origins of life.
The question of how codons came to be associated with specific amino acids in the present form of the genetic code is one fundamental part of gaining insight into the origins of life. Carl Woese and coworkers designed a series of experiments to test associations between amino acids and nucleobases that may have played a role in establishing the genetic
code. Through these experiments it was found that a property of amino
acids called the polar requirement (PR) is correlated to the organization of the codon table. No other property of amino
acids has been found that correlates with the codon table as well as PR, indicating that PR is uniquely related to the
modern genetic code. Using molecular dynamics simulations of amino acids in solutions of water and dimethylpyridine used to experimentally measure PR,
we show
that variations in the partitioning between the two phases as described by radial distribution functions
correlate well with the measured PRs. Partition coefficients based on probability densities of the amino acids in each phase have the linear behavior with base concentration as suggested by the PR experiments.
We also investigate the possible roles of inorganic mineral surfaces in catalysis and stabilization of reactions essential for early forms of replicating systems that could have evolved into biochemical processes we know today. We study a proposed origins of life scenario involving the clay montmorillonite, as well as a generalized form of a charged surface, and their catalytic role in forming oligonucleotides from activated mononucleotides. Clay and mineral surfaces are important for concentrating the reactants and for promoting nucleotide polymerization reactions. Using classical molecular dynamics methods we provide atomic details of reactant conformations prior to polynucleotide formation, lending insight into previously reported experimental observations of this phenomenon. The simulations clarify the catalytic role of metal ions, demonstrate that reactions leading to correct linkages take place primarily in the interlayer, and explain the observed sequence selectivity in the elongation of the chain. The study comparing reaction probabilities involving L- and D- chiral forms of the reactants has found enhancement of homochiral over heterochiral products when catalyzed by montmorillonite.
Finally, we shift our perspective on the problem of the origins of life, by considering a modern biological reaction which is essential to all forms of life today: the charging of tRNA with correct amino acids according to their anticodons. These reactions are performed by amino-acyl tRNA synthetases (AARSs), and are essential for enforcing the genetic code. While studies involving the PR and code optimality apply to a more error-prone epoch of early biology, possibly forming ``statistical proteins" whose sequence is determined probabilistically by a loose mechanism of assignment of amino acids based on (possibly) PR, the mechanisms that charge tRNA today are highly refined to charge only the correct amino acid to a tRNA, and are thus essential for the high-fidelity translation mechanism present in all living cells. To gain some insight into how the charging reaction may have come about, we apply quantum chemical methods to a problem of modern biology to gain a further understanding of the mechanisms behind biochemical reactions
