Membrane Catalysed Formation of Nucleotide Clusters and Its Role in the Origins of Life

Abstract

One of the mysteries in studying the molecular “Origin of Life” is the emergence of RNA and RNA-based life forms, where non-enzymatic polymerization of nucleotides is a crucial hypothesis in formation of large RNA chains. The non-enzymatic polymerization can be mediated by various environmental settings such as cycles of hydration and dehydration, temperature variations and proximity to a variety of organizing matrices such as clay, salt, fatty acids, lipid membrane and mineral surface. In this work, we explore the influence of different phases of the lipid membrane towards nucleotide organization and polymerization in a simulated prebiotic setting. We calculate the free energy cost of localizing a mononucleotide, Uridine monophosphate (UMP), in distinct membrane settings and we perform all-atom molecular dynamics (MD) simulations to estimate the role of the monophasic and biphasic membrane in modifying the behavior of UMPs localization and their clustering mechanism. Based on the free-energy and diffusion data from our MD calculations, we develop a lattice based model to explore the thermodynamic limits of the observations made from the MD simulations. The mathematical model substantiates our hypothesis that the lipid layers can act as unique substrates for ‘catalyzing’ polymerization of mononucleotides due to the inherent spatiotemporal heterogeneity and phase change behavior.