Higher Permeability of l-Ribose Versus d-Ribose through Prebiotically-Relevant Lipid Bilayers Measured by Molecular Dynamics Simulations Challenges Origin of Life Models for the Generation of D-RNA

Membrane permeability has been suggested as a contributing factor in the prebiotic selection of d-ribose as the sugar component of nucleic acid polymers. Experimental work has demonstrated that d-ribose permeates through fatty acid bilayers faster than several diastereomers, but permeation of the enantiomer l-ribose was not experimentally tested. Here, we used molecular dynamics simulations to calculate the permeability coefficients of β-d-ribopyranose and three aldopentose stereoisomers through fatty acid bilayers of varying length and composition, including two bilayers specifically composed to mimic the range of short chain amphiphiles assumed to be present in prebiotic scenarios. The permeation rate of aldopentose stereoisomers through oleic acid bilayers, myristoleic acid bilayers, and 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers, correlates with experimental permeability measurements. In these three bilayers, β-d-ribopyranose and β-l-ribopyranose permeated similarly. By contrast, in short chain bilayers containing mixtures of lauric acid, myristic acid, and myristoleic acid, β-l-ribopyranose diffused across the membrane between 2-fold and 3-fold faster than β-d-ribopyranose. The rate of intramolecular hydrogen bonding interactions formed during permeation was similar between the two enantiomers. These results imply that the interior of protocells likely contained both enantiomers of ribose and assembled a mixture of heterochiral and homochiral nucleic acid polymers, which would slow down replication and greatly increase consumption of nucleotides. Thus, passive membrane permeation alone cannot select for β-d-ribopyranose in putative prebiotic models, and that competition by β-l-ribopyranose for inclusion in early nucleic acid polymers must be considered in models of protocell evolution.