Protobiotic Systems Chemistry Analyzed by Molecular Dynamics

Abstract

Systems Chemistry has been a key component of origin of life research, invoking models of life’s inception based on evolving molecular networks. One such model is the Graded Autocatalysis Replication Domain (GARD) formalism embodied in a Lipid World scenario, which offers rigorous computer simulation based on defined chemical kinetics equations. GARD suggests that the first pre-RNA life-like entities could have been homeostatically-growing assemblies of amphiphiles, undergoing compositional replication and mutations, as well as rudimentary selection and evolution. Recent progress in Molecular Dynamics has provided an experimental tool to study complex biological phenomena such as protein folding, ligand-receptor interactions and micellar formation, growth and fission. The detailed molecular definition of GARD and its inter-molecular catalytic interactions make it highly compatible with Molecular Dynamics analyses. We present a roadmap for simulating GARD’s kinetic and thermodynamic behavior using various Molecular Dynamics methodologies. We review different approaches for testing the validity of the GARD model, by following micellar accretion and fission events and examining compositional changes over time. Near future computational advances could provide empirical delineation for further system complexification, from simple compositional non-covalent assemblies towards more life-like protocellular entities with covalent chemistry that underlies metabolism and genetic encoding.

Combinatorial Fusion Rules to Describe Codon Assignment in the Standard Genetic Code

“…Observations indicate that triplet/amino acid affinities are highest for amino acids that presumably integrated earliest the genetic code. Presumed “more recent” amino acids have low affinities for their assigned nucleotide triplets [ 81 ]. We compare the affinities for the three primordial partition AU/GC, AG/CU, and the AC/GU, using the values as reported previously [ 51 ].…”

One‐carbon metabolism, folate, zinc and translation

“…This modification allows sequestering of folate within the cell, and, as witnessed in thioester‐dependent syntheses using 4‐phosphopantetheine, it may serve as a swinging arm that permits metabolic channelling of the cofactor between successive folate‐dependent enzymes or catalytic centres (Schirch and Strong, 1989). Unravelling the possible scenarios coupling all these pathways together in an autocatalytic cycle (Kahana and Lancet, 2019) is out of the scope of the present work. Let us simply assume that, at some point, these processes resulted in the folate‐dependent synthesis of methionine following one of the many pathways involving the protection/ deprotection steps that are still distributed among extant organisms that make methionine (Ferla and Patrick, 2014; Bastard et al , 2017).…”

Progress in integrative systems biology, physiology and medicine: towards a scale-relative biology

“…8b showing a division process, reflects the synthetic cell as an autopoietic system [211]; (iii) A chargeinduced fractal network (a macroscopic path integral) represents an essential ingredient for the emergence of a coherent macroscopic quantum-like system that underpins autopoiesis, which could not have emerged from a classically ordered structure such as a liposome; (iv) With scale relativity, we have a clearly described physical theory and mathematical framework available to account for the experimental exemplars of closure of constraints and autopoiesis. Both theory and experiment represent a step change beyond earlier theoretical biology studies on autopoiesis [209][210][211], and others that emphasise the possible role of protein or lipid soups with autocatalytic properties in the formation of protocellular assemblies [212][213][214][215].…”