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.

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).…”

Molecules to Microbes

“…Lancet estimates this may have taken place several hundreds of millions of years after the Earth cooled down, to reach the Last Universal Common Ancestor (LUCA) at just prior to 3.5 billion years ago. The latter time frame being the point at which the existence of fossils pertaining to the unicellular life forms have been confirmed with a degree of certainty [28][29][30][31].…”

Footprints of a Singular 22-Nucleotide RNA Ring at the Origin of Life

“…At last, a number of recent models have pointed to the role of a lipid component in the very early stages of the origin of RNA structures [17][18][19][20][21], which secondarily could have functioned independently [22]. Another possibility is that those lipids may result from the apparition of proteins catalyzing their synthesis, as in Archaea where a number of enzymes contribute to the biosynthesis of lipids [23].…”