arXiv subjects

Louie Slocombe

Publications and source records attributed to Louie Slocombe.

7 recordsLinked to original sources

arXiv2026

Assembly Spaces: Formal Definitions and Fast Methods for Approximating Assembly Indices

Assembly theory is an experimental and theoretical framework that introduces a metrological approach to detecting life, with potential applications across diverse substrates. Its two central observables are assembly index and copy number. The assembly index is the minimum number of joining operations required to construct an object from its elementary parts; for molecules, it can be measured using mass spectrometry, infrared spectroscopy, and NMR. Copy number is the abundance of a given distinguishable object within a sample. A key empirical result of the theory is that high assembly index combined with high copy number constitutes a signature that cannot arise abiotically, and this has been validated experimentally in application to molecular biosignatures. The foundational theoretical concept underlying these results is the assembly space, which encodes the causal possibilities determinable from observed objects, with the assembly index the shortest path to them given the physical constraints of a given substrate. Here, we provide a generalized formalism to describe assembly spaces and tools for assembly index approximations. We begin by reviewing the applications of assembly theory across molecules, minerals and atmospheres, and then introduce a general, substrate-independent formal definition of assembly spaces and assembly indices. We develop a unified path hierarchy framework to clarify relationships among the various representations of assembly spaces and assembly paths that appear in the literature on molecular assembly. Finally, we show how formal grammar algorithms can be adapted to efficiently bound assembly index calculations and provide clarification on the utility of such approximations, with the goal to increase the accessibility of tools to explore this emerging area for a broader group of researchers across chemistry, biology, and complexity science.

cs.FL↗

arXiv2026

Deep-time consistency in proteome elemental composition across cellular and viral life

Proteins are constructed from a limited alphabet of ~20 amino acids, yet the origins and selection of this specific alphabet are unresolved. One largely overlooked aspect is whether elemental composition constrains the range of viable proteomes. Here, we analyze the elemental composition of thousands of proteomes spanning cellular domains and viral realms. Despite evolutionary divergence and orders-of-magnitude variation in proteome size and gene content, proteomes exhibit strikingly consistent elemental composition. This consistency is substantially more constrained than amino acid frequencies or physicochemical properties and is not explained by evolutionary relatedness, biological function, or amino acid usage alone. Viral proteomes occupy the same elemental composition space observed in cellular organisms despite the absence of a single viral common ancestor, suggesting common biochemical constraints shape proteome organization across life. To investigate the evolutionary origins of this pattern, we compare modern proteomes with multiple independent reconstructions of the Last Universal Common Ancestor (LUCA) and with synthetic reduced-alphabet proteomes generated from primordial amino acid alphabets. LUCA proteomes occupy the same constrained elemental composition space observed in modern Bacteria and Archaea, whereas reduced primordial-like alphabets systematically generated alternative elemental regimes outside the modern range despite retaining high sequence similarity to extant proteins. Reduced alphabets disrupt fold space and reorganize relationships between elemental composition and predicted protein structural organization. Our results suggest that constrained elemental composition represents a fundamental organizational property of proteomes, which emerged early in evolution and may have contributed to the selection and stabilization of the modern amino acid alphabet.

q-bio.BM↗

arXiv2026

Searching for Life-As-We-Don't-Know-It: Mission-relevant Application of Assembly Theory for Exoplanet Life Detection

This white paper introduces a framework for applying Assembly Theory (AT) to planetary atmospheres as a biosignature framework suitable for the Habitable Worlds Observatory (HWO). AT quantifies the minimum combinatorial complexity required to co-construct an observed ensemble of molecular species, providing a measure of how much selection and evolution is encoded in a planetary atmosphere's chemical space, without assuming any specific biochemistry, kinetics nor metabolism. We outline some forthcoming results applying this framework and how it can be extended to population-level exoplanet studies, validated against existing spectroscopic data, and used to directly inform HWO instrumental requirements. Rather than imposing a binary alive/dead classification, AT-based atmospheric analysis would provide a continuous measure of planetary complexity, opening a path toward detecting life-as-we-don't-know-it.

astro-ph.IM↗

arXiv2025

Conformational Dynamics of 8-Oxoguanine Mispairing Reveal a Mechanism of Polymerase {\lambda} Misincorporation

Experimental evidence has shown the stability of oxygen-stress-damaged guanine, known as 8-oxoguanine. This common oxygen-damaged nucleobase is often found in the presence of reactive oxygen species and can result in the mispairing between adenine and 8-oxoguanine in a Hoogsteen pair. We have computationally investigated the role of 8-oxoguanine to support experimental results and focus the investigation towards the polymerase structure, identifying how 8-oxoguanine interacts in the polymerase environment. Quantum mechanical investigations show the Hoogsteen pairing of adenine and 8-oxoguanine is the most energetically favourable state compared to a Watson-Crick state, supporting experimental evidence. Molecular Dynamical calculation of 8-oxoguanine located in B-DNA provide an average C1' backbone spacing of 1.1 nm compared to adenine-thymine spacing of 1.05 nm but remains within the error margin, however when in the polymerase environment, 8-oxoguanine and the canonical adenine - thymine spacing match at 1.11-1.12nm spacing while 8-oxoguanine is located on the template strand, but is disrupted by tyrosine 251 while situated on the triphosphate strand. We observe that 8-oxoguanine, when paired with adenine in polymerase {\lambda}, can mimic the adenine-thymine structure, as predicted in experimental results, and thus would be misincorporated, but is strongly dependent on its conformation.

physics.bio-ph↗

arXiv2025

The Emergence of Chirality from Metabolism

Molecular chirality is critical to biochemical function, but it is unknown when chiral selectivity first became important in the evolutionary transition from geochemistry to biochemistry during the emergence of life. Here, we identify key transitions in the selection of chiral molecules in metabolic evolution, showing how achiral molecules (lacking chiral centers) may have given rise to specific and abundant chiral molecules in the elaboration of metabolic networks from geochemically available precursor molecules. Simulated expansions of biosphere-scale metabolism suggest new hypotheses about the evolution of chiral molecules within biochemistry, including a prominent role for both achiral and chiral compounds as nucleation sites of early metabolic network growth, an increasing enrichment of molecules with more chiral centers as these networks expand, and conservation of broken chiral symmetries along reaction pathways as a general organizing principle. We also find an unexpected enrichment in large, non-polymeric achiral molecules. Leveraging metabolic data of 40,023 genomes and metagenomes, we analyzed the statistics of chiral and achiral molecules in the large-scale organization of metabolism, revealing a chiral-enriched phase of network organization evidenced by system-size dependent chiral scaling laws that differ for individuals and ecosystems. By uncovering how metabolic networks could lead to chiral selection, our findings open new avenues for bridging metabolism and genetics-first approaches to the origin of chirality, allowing tools for better timing of major transitions in molecular organization during the emergence of life, understanding the role of chirality in extant and synthetic metabolisms, and informing targets for chirality-based biosignatures.

q-bio.MN↗

arXiv2025

Single-Molecule Water Motion on h-BN and Graphene: A Paradigm Shift in Understanding the Behaviour of Water on 2D Material Interfaces

Understanding water behaviour on 2D materials is crucial for sensing, microfluidics, and tribology. While water/graphene interactions are well studied, water on hexagonal boron nitride (h-BN) remains largely unexplored. Despite structural similarity to graphene, h-BN's slightly polar B-N bonds impart a large band gap, high thermal conductivity, and chemical stability, making it promising for electronics, lubricants, and coatings. Moreover, existing water studies often focus on multilayer water dynamics, overlooking single-molecular details. We bridge this gap by studying single-molecular water friction and diffusion on h-BN, comparing it with graphene using helium spin-echo experiments and ab initio calculations. Our findings show that water diffusion on h-BN/Ni follows a complex rotational-translational dynamic, unlike graphene. While conventional views treat water motion as discrete jumps between equivalent adsorption sites, we demonstrate that on h-BN, water molecules rotate freely around their centre of mass. Although the binding energies of water on h-BN and graphene are similar, the activation energy for water dynamics on h-BN is 2.5 times lower than on graphene, implying a much lower barrier for molecular mobility. The fundamentally different diffusion characteristics which classical models cannot capture, underscores the need to rethink how we model water on polar 2D materials. Moreover, our analysis reveals that the metal substrate strongly influences water friction, with h-BN/Ni showing a markedly lower friction than graphene/Ni, in stark contrast to the free-standing materials. These findings challenge assumptions about 2D material-water interactions, highlighting the crucial role of substrate effects in chemistry and material science and offer insights for designing next-generation microfluidic devices that require precise water mobility control.

cond-mat.mes-hall↗

arXiv2021

An Open Quantum Systems approach to proton tunnelling in DNA

One of the most important topics in molecular biology is the genetic stability of DNA. One threat to this stability is proton transfer along the hydrogen bonds of DNA that could lead to tautomerisation, hence creating point mutations. We present a theoretical analysis of the hydrogen bonds between the Guanine-Cytosine (G-C) nucleotide, which includes an accurate model of the structure of the base pairs, the quantum dynamics of the hydrogen bond proton, and the influence of the decoherent and dissipative cellular environment. We determine that the quantum tunnelling contribution to the process is several orders of magnitude larger than the contribution from classical over-the-barrier hopping. Due to this significant quantum contribution, we find that the canonical and tautomeric forms of G-C inter-convert over timescales far shorter than biological ones and hence thermal equilibrium is rapidly reached. Furthermore, we find a large tautomeric occupation probability of $1.73\times 10^{-4}$, suggesting that such proton transfer may well play a far more important role in DNA mutation than has hitherto been suggested. Our results could have far-reaching consequences for current models of genetic mutations.

physics.bio-ph↗