<div>Non-enzymatic polymerisation explained how life could assemble spontaneously on the early Earth. Prior research has discovered that the non-enzymatic polymerisation can be mediated by various environmental settings, most widely accepted are the reactions driven by the cycles of hydration and dehydration and organising matrices such as clay, salt, membranes and mineral surface. Membranes have a unique feature which prepares it as a sensitive organising matrix, as compared to mineral surface and clay, which transforms its phase with small changes in temperature, hydration and composition of lipids. Multi-component membranes can show phase separation where two or more distinct phases can co-exist. To the best of our knowledge, this is for the fi?rst time the influence of different phases of the membrane in the nucleotide organisation and polymerisation in a simulated prebiotic setting in this work have been explored. This study encompasses the energetics of inserting a mononucleotide, UMP, in distinct membrane settings which is probed utilising the PMF. The preferential partitioning of UMP is also investigated; which is coupled to the location of the insertion and the composition of the PSM/DOPC/Chol membranes. Combined with umbrella-sampling calculations, AA-MD simulations were performed to estimate the role of the</div><div>monophasic and diphasic membrane in modifying the behaviour of UMPs and their clustering mechanism. A mathematical model was also developed based on lattice model and random walk and some of the parameters were trained from the AA-MD simulations. The results indicated that the membranes were capable of concentrating nucleotides and organised into anisotropic clusters, and the thermodynamic studies along with mathematical model showed that it had a sharp preference for the Lo/Ld domain interface for clustering.</div>

<div>Non-enzymatic polymerisation explained how life could assemble spontaneously on the early Earth. Prior research has discovered that the non-enzymatic polymerisation can be mediated by various environmental settings, most widely accepted are the reactions driven by the cycles of hydration and dehydration and organising matrices such as clay, salt, membranes and mineral surface. Membranes have a unique feature which prepares it as a sensitive organising matrix, as compared to mineral surface and clay, which transforms its phase with small changes in temperature, hydration and composition of lipids. Multi-component membranes can show phase separation where two or more distinct phases can co-exist. To the best of our knowledge, this is for the fi?rst time the influence of different phases of the membrane in the nucleotide organisation and polymerisation in a simulated prebiotic setting in this work have been explored. This study encompasses the energetics of inserting a mononucleotide, UMP, in distinct membrane settings which is probed utilising the PMF. The preferential partitioning of UMP is also investigated; which is coupled to the location of the insertion and the composition of the PSM/DOPC/Chol membranes. Combined with umbrella-sampling calculations, AA-MD simulations were performed to estimate the role of the</div><div>monophasic and diphasic membrane in modifying the behaviour of UMPs and their clustering mechanism. A mathematical model was also developed based on lattice model and random walk and some of the parameters were trained from the AA-MD simulations. The results indicated that the membranes were capable of concentrating nucleotides and organised into anisotropic clusters, and the thermodynamic studies along with mathematical model showed that it had a sharp preference for the Lo/Ld domain interface for clustering.</div>

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.