The Revolution Evolution

A major contribution to the progress in structural biology was accomplished thanks to the advances in cryo-EM, coined the Resolution Revolution. Currently, we are witnessing the development of powerful computational tools for structure prediction: AlphaFold2 and RoseTTAFold. However, photosynthetic complexes represent a major challenge due to additional levels of complexity arising from their multi-protein nature and the role in sunlight-driven energy conversion. They reside in a lipid bilayer and bind dozens or sometimes hundreds of pigments for light harvesting: chlorophylls, carotenes, xanthophyll and more. Thus, protein–protein interaction networks are intricate, and frequently involve lipids and other cofactors. In addition, the association of chlorophylls is highly specific and most probably occurs concomitantly with protein folding. The recent advances in model refinement methods need further development to serve the requirements of the plant sciences. This is particularly important in the context of cofactors, as cryo-EM is the only empirical method to identify individual bound lipids and pigments that are essential for function.

Today, experimental scientists have the privilege of freely accessing the generous PDB resource with its enormous amount of information, and of use high-resolution cryo-EM data to form molecular models that in turn will be used by computational scientists to further expand the repertoire of the protein space tomorrow. However, the field of photosynthetic complexes remains a less explored territory due to the complexity, diversity and abundance of the non-protein components involved. Whether one prefers to co-opt the term revolution or evolution to describe the process of entering unseen worlds of molecules through the paths of the PDB, cryo-EM or structure prediction, each one of those accomplishments has contributed a new substance and concept that evolved into technical advances that have shaped the structural biology approach. Capturing those precious moments as an active scientist is a privilege. And the history of research teaches us that it is also an opportunity to nurture transformative approaches, explore new fields and form accurate models of reality.