Computational Exploration of Lipid Chemical Space: Predicting Assembly Using QSPR Models

Kurzfassung

Compartmentalization is likely to have been essential for the emergence of life. Compartmentalization allows for the creation of unique chemical conditions that can be maintained out of equilibrium with the environment and the exclusion of parasites. Confining organic molecules also helps limit diffusion, increases concentration and can thus influence both the thermodynamics and kinetics of prebiotic reactions. Biology currently predominantly uses phospholipids to construct cell membranes. However, there are many other types of organic compounds that can form stable compartments in water, and many of these may have been abundant in the prebiotic environment. In this study we explore this alternative lipid chemical space by using structure enumeration algorithms to compute an exhaustive combinatorial library of surfactant molecules. We then predict the propensity of these compounds to self-assemble into membranes using quantitative structure-property relationship (QSPR) models on critical micelle concentration (CMC). Combined with critical packing parameter calculations, these models can allow identification of novel molecule types which can be experimentally assayed as candidates for the emergence of protocells.