Scientists used computer experiments to model the lipids used in COVID-19 vaccines

The theoretical study was published on the cover of The Journal of Physical Chemistry Letters.

mRNA vaccines cannot do without lipid nanoparticles. They form a protective coating around the mRNA and ensure its safe transport into human cells.

“The computer simulations we run can provide unique information about the behaviour of highly complex molecular systems, with atomic resolution. The beauty of the simulations is that it is relatively easy to adjust the systems we are studying, changing conditions and composition. With the help of supercomputers, we can perform experiments that are difficult to imagine in practice, and obtain valuable information that can then be used, for example, to design new ‘delivery envelopes’ for cell therapies,” said one of the authors, Michal Otyepka, who works at both research centres.

Computational chemists created various models of lipid mixtures, ranging from simple bilayers to complex systems, on the supercomputer at the IT4Innovations Centre in Ostrava. They also played with the pH setting, as the ionisable lipids used change their charge and properties when the pH changes.

“We found that ionisable lipids, i.e. the nanoparticle-specific lipids in vaccines, behave differently than the common lipids we have in our bodies. They do not form simple membranes, but rather disordered 3D structures. They also do not form a homogeneous mixture with other lipids, but ionisable lipids create a special phase that subsequently interacts with RNA,” said study co-author Markéta Paloncýová from CATRIN.

The study of lipids in the context of mRNA vaccines is being pursued, among other things, in an attempt to find a compromise on their stability. This must be sufficient for RNA delivery, but at the same time lipids must be prevented from accumulating in the body.

A long-term goal of computational chemists is to understand exactly what lipids and their structural elements cause and how they affect the properties of vaccine. Its universal functioning in the body is known, but getting to atomic resolution is not possible to achieve during experiments. Simulations provide this insight. While in this study, the experts were only able to model a small part of the nanoparticle, in the future they would like to model a representation of the whole nanoparticle and conduct multi-scale modelling. Understanding the interactions between RNA and lipids at the atomic level may lead to the design of better lipid nanoparticle compositions and thus the properties of vaccines and other RNA-based drugs.