Quantifying Mineral-ligand Structural Similarities: Bridging the geological world of Minerals with the Biological World of Enzymes

Abstract:

Metal compounds abundant in 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 for 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 and chemical similarities between various minerals and ligands using molecular similarity metrics. We use an iterative substructure search in the crystal lattice, paired with benchmark chemical similarity methods. Since such similarity metrics are largely successful in predicting substrate substitutions for drug-target interactions, its potential application in predicting the catalytic role of minerals is significant. Our approach aims to detect relationships between the mineral and enzyme worlds, with applications to the origins of life, ecology, catalysis and astrobiology. Preliminary results are encouraging.