Principal component analysis highlights the influence of temperature, curvature and cholesterol on conformational dynamics of lipids.

Membrane lipids are inherently highly dynamic molecules. Currently, it is difficult to probe the structures of individual lipids experimentally at the timescales corresponding to atomic motions, and consequently molecular dynamics simulations are used widely. In our previous work, we have introduced the principal component analysis (PCA) as a convenient framework for comprehensive quantitative description of lipid motions. Here, we present a newly developed open source script, PCAlipids, which automates the analysis and allows us to refine the approach and test its limitations. We use PCAlipids to determine the influence of temperature, cholesterol and curvature on individual lipids, and show that the most prominent lipid tail scissoring motion is strongly affected by these factors and allows tracking of phase transition. Addition of cholesterol affects the conformations and selectively changes the dynamics of lipid molecules, impacting the large-amplitude motions. Introduction of curvature biases the conformational ensembles towards more extended structures. We hope that the developed approach will be useful for understanding the molecular basis of different processes occurring in lipid membrane systems and will stimulate development of complementary experimental techniques probing the conformations of individual lipid molecules.