Genomics, Proteomics, Bioinformatics

Compositional Diversity Of Minimal Coacervates In A Nucleic Acid-peptide World

By Keith Cowing
Status Report
chemrxiv.org
November 8, 2024
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Compositional Diversity Of Minimal Coacervates In A Nucleic Acid-peptide World
In silico investigations reveal contact modes and frequency of interactions in peptide/nucleic acid coacervates. (a) Representative simulation snapshot of the R4/RNA8 mixture, showing a cluster of RNA and peptide, and unbound peptide in excess. Inset magnifications highlight the investigated interaction modes, e.g., hydrogen bonding, electrostatic interactions, and π-π/cation-π stacking. (b) Comparison between the number of DNA and RNA interactions with arginine peptides (per frame, per nucleotide), separated into three categories: hydrogen bonding, electrostatic interactions and stacking. (c) Simplified rendering of R4/DNA8 (blue) and R4/RNA8 (purple) clusters, showing the helical, structured conformation acquired by DNA strands and the more disordered folding acquired by RNA strands, which leaves ribonucleotides exposed to interact with peptides. (d) Number of peptide/oligonucleotide contacts (all modes of interaction), which represents the total number of intermolecular contacts that one molecule of RNA8 or DNA8 forms with R3 or R4. (e) Excess peptide remaining in the simulation box at equilibrium for RNA8 or DNA8 coacervates with R3 or R4. Abbreviations: R = Arginine. — chemrxiv.org

The early co-evolution of RNA and peptides is at the core of the RNA-peptide world hypothesis. Recent studies suggest that nucleotides and amino acids could have formed and polymerised non-enzymatically under prebiotic conditions, generating short oligonucleotides and peptides capable of non-enzymatic RNA replication and peptide synthesis.

However, whether the cooperation between nucleic acids and peptides stems from their co-localisation in primitive compartments is unclear. Here we demonstrate the early and likely inevitable emergence of primitive coacervates via liquid-liquid phase separation of prebiotic heterogeneous mixtures of short non-coded oligonucleotides and peptides.

We show that peptide/nucleic acid coacervates are more prone to form than peptide/peptide coacervates, and that peptide/RNA coacervates are remarkably more stable than peptide/DNA coacervates. Atomistic simulations confirm that the more extended and less structured conformation of RNA over DNA enables more contact points with peptides.

The more abundant interactions in peptide/RNA coacervates lead to enhanced salt and thermal stability, yet reduced fluidity compared to their DNA counterparts – which are in turn capable to fully preserve RNA secondary structure upon partitioning.

Our findings suggest that peptide/oligonucleotide co-localisation via coacervation would have inevitably occurred at an early stage of a more holistic nucleic acid-peptide world scenario. Both RNA and DNA would have thus been required to ensure the emergence of coacervates with balanced stability and fluidity to host non-enzymatic RNA chemistry.

Compositional diversity of minimal coacervates in a nucleic acid-peptide world, chemrxiv.org

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