Quantifying Mineral-Ligand Structural Similarities: Bridging the Geological World of Minerals with the Biological World of Enzymes

Abstract

Metal compounds abundant on Early Earth are thought to play an important role in the origins of life. Certain iron-sulfur minerals for example, are proposed to have served as primitive metalloenzyme cofactors due to their ability to catalyze organic synthesis processes and facilitate electron transfer reactions. An inherent difficulty with studying the catalytic potential of many metal compounds is the wide range of data and parameters to consider when searching for individual minerals and ligands of interest. Detecting mineral-ligand pairs that are structurally analogous enables more relevant selections of data to study, since structural affinity is a key indicator of comparable catalytic function. However, current structure-oriented approaches tend to be subjective and localized, and do not quantify observations or compare them with other potential targets. Here, we present a mathematical approach that compares structural similarities between various minerals and ligands using molecular similarity metrics. We use an iterative substructure search in the crystal lattice, paired with benchmark structural similarity methods. This structural comparison may be considered as a first stage in a more advanced analysis tool that will include a range of chemical and physical factors when computing mineral-ligand similarity. This approach will seek relationships between the mineral and enzyme worlds, with applications to the origins of life, ecology, catalysis, and astrobiology.

‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life

“…In almost all scenarios for the origin of life, both terrestrial and marine, the initial catalysts are assumed to have involved transition metals particularly Fe and Ni with sulphur ( Table 2 , property 9) [ 16 , 51 , 135 , 137 , 151 , 152 , 153 ], although more recently a wider net has been cast [ 154 , 155 ]. Their antiquity is supported by the prevalence of ferredoxins, with their Fe(Ni)S centers, in metabolic pathways [ 16 , 51 , 135 , 152 ] ( Figure 4 , step 1b).…”

What are inorganic nanozymes? Artificial or inorganic enzymes

“…95,147,168,[240][241][242] It is interesting to note that several researchers, particularly geochemists, have developed various hypotheses linking mineral structures to the metal centers of specific enzymes. 63,153,154,163,[243][244][245][246][247][248][249][250][251] The fact of the enzyme-like activity of inorganic nanomaterials implies that metalloenzymes are probably derived from inorganic nanozymes with the same metal center. It is, in essence, the result of natural selection and evaluative processes related to structural stabilization.…”

Inorganic Fe-O and Fe-S oxidoreductases: paradigms for prebiotic chemistry and the evolution of enzymatic activity in biology

“…This hypothesis is supported by research on hydrothermal vents that mimic conditions that may have been present at the onset of living organisms ( Baross and Hoffman, 1985 ; Russell and Hall, 1997 ; Nitschke and Russell, 2009 ). The Fe-S clusters in proteins exhibit considerable similarity to various iron sulfides ( Zhao et al, 2020 ; McGuinness et al, 2022 ). Relevant examples include eukaryotic ferredoxins and Rieske proteins that contain a Fe-S cluster with two Fe and two S atoms forming a 2Fe-2S diamond ( Holden et al, 1994 ; Gurbiel et al, 1996 ), while higher potential iron-sulfur proteins and iron regulatory proteins (IRPs) use four Fe and four S atoms to form a cubic 4Fe-4S cluster ( Breiter et al, 1991 ; Solomon et al, 2000 ; Dupuy et al, 2006 ; Imlay, 2006 ).…”