Fool's gold: Ligand–receptor interactions and the origins of life

The origins of life is a question that continues to intrigue scientists across disciplines. The hypothesis that life began with a simple form of metabolism is constrained by the lack of necessary enzymes to catalyze reactions such as carbon fixation. Other catalytic mechanisms have been suggested, with mineral surfaces and metals offering the redox “spark” essential to prebiotic chemistry. There has also been some suggestion that the binding affinity of the ligands synthesized in this pre-enzymatic metabolism acted as an early version of natural selection: more strongly binding ligands were accumulated into further autocatalytic reactions and the aggregation of complex biological materials. Ligand–receptor binding is thus fundamental to the origins of life. In this paper, we use the origins of life theory as a lens through which to review ligand–receptor interactions as they are more commonly understood today. In particular, we focus on the electron tunneling theory of receptor activation that has emerged from research into quantum biology. We revisit criticism against this theory, particularly the lack of evidence for electron transfer in receptors, to see what insights are offered by ligand–receptor interactions mediated by iron sulfur compounds at the origins of life. What emerges from this comparison is the central importance of redox activity in receptors, in particular, with respect to the recurring presence of the disulfide bond. While the paper is a speculative exercise, we conclude that conductivity in biomolecules, particularly the selective conductivity conferred by appropriate ligand–receptor binding, may be a powerful tool for understanding diverse phenomena such as pharmacological potency and viral infection.