Computational predictions of the aggregation of amphiphiles for early compartmentalisation

Abstract

The formation of compartments, through which an internal environment is separated from its surrounding medium, is essential for all modern life. Compartmentalisation enables specific molecules to be concentrated, thus facilitating biochemistry. The existence of individuals also facilitates competition for survival, and provides a driving force for evolution. Modern cell membranes are incredibly complex structures, containing a myriad of lipid species, alongside various structural and functional proteins. However, protocells may not have had access to or required such a wide range of components to survive. Therefore the earliest membranes may have been composed of simple amphiphiles or simple mixtures of amphiphiles. A number of computationally intensive methods have proved ineffective at predicting the properties of these systems and so we developed chemoinformatics approaches to try to uncover the essential requirements for such molecules. Methods for generating compound libraries will be described as well as refinements to reduce the number of molecules generated or to control the similarity of the molecules to the known lipids of modern biology. The goal of this work is to understand which classes of simpler amphiphiles can self-assemble to form compartments and what the properties of the earliest membranes may have been. The limited molecular complexity of these amphiphiles may have enabled a variety of adaptive physical properties, such as enhanced permeability. Whilst this may compromise the level of protection from the external environment compared with modern biology, more permeable barriers could have facilitated more rapid introduction of greater diversity of chemical species and process. The generation of a novel large-scale library provides excellent coverage of chemical space, and the characterisation of these molecules provides insight into the aggregation properties of these chemical species.