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.

Minerals as Prebiotic Catalysts for Chemical Evolution towards the Origin of Life

“…Many prebiotic syntheses are influenced by similar perceptions and pursue the prebiotic carbon and nitrogen fixation using enzyme mimetic mineral catalysts [27,45,48,49,51,52,54,69]. This idea could narrow down the candidates of geo-catalysts, however, an inherent difficulty in studying the property of minerals is the wide range of data and parameters to consider when searching for an appropriate catalyst for a specific enzymatic reaction [91]. Especially, since the structure (particularly the first coordination structure) alone doesn't dictate the overall catalytic property, the structural resemblance between minerals and enzymes doesn't ensure a definite functional similarity.…”

“…To solve this problem, a computational approach has been employed to systematically compare the metal-ligand structure of minerals and enzymes, as reported in recent work by Zhao et al [91]. They compared the metalloenzyme cluster structure recorded in the protein database and the mineral structural data in the mineralogy database, using molecular similarity metrics.…”

Unravelling the Structural Development of Peptide‐Coordinated Iron‐Sulfur Clusters: Prebiotic Evolution and Biosynthetic Strategies

“…Fe‐S centers in minerals and clusters not only share functional links with extant metalloproteins, but also exhibit structural similarities. [ 68‐69 ] Though many controversial hypotheses were proposed throughout decades, we are now at the turning point of systematic, quantitative comparisons, aiming to establish complete connections between the structures of minerals and metalloenzyme clusters. A latest research utilized a mathematical method to survey iterative substructure in the crystal lattice and benchmark structural similarity, which synthetically bridges the gap between iron sulfide minerals and simple enzymes (Figure 6).…”

“…A latest research utilized a mathematical method to survey iterative substructure in the crystal lattice and benchmark structural similarity, which synthetically bridges the gap between iron sulfide minerals and simple enzymes (Figure 6). [ 69 ] Ferrodoxins are considered one of the most ancient metalloproteins in the biosphere, [ 30,70‐71 ] which make use of three classical Fe‐S clusters: [2Fe‐2S], [3Fe‐4S], and [4Fe‐4S], and all three of…”

“…A set of mineral‐enzyme structural comparisons using similarity index (number above arrows). Reproduced with permission from ref 69. Copyright 2020 MDPI.…”