Authors of the study: Teruaki Koto (PhD, research fellow) and Tibor Páli (DSc, PI) of the new Molecular Biophysics Research Group at the Institute of Biophysics.

Bacteriophages (shortly phages) are viruses that infect and replicate only in bacterial cells. They are ubiquitous in the planet, extremely diverse in size, morphology, and genomic organisation, and they are the earth's most abundant biological agent. As being harmless to human cells but killing bacteria, they are subject of intense studies (also in the HUN-REN BRC) as potential alternative therapeutic tools for fighting bacteria and their increasing resistance against drugs. Therefore, the genome-structure-function relationship of phages is of great interest. However, the atomic structure of complex biomolecular assemblies (such as viruses) with millions or billions of atoms are still out of reach experimentally, and also predicting, building or even displaying their all-atom models still represent great challenge due to the enormous data size, the required complex procedures and the limitations of graphics hardware when presented with a huge number of graphical objects. (Only imaginary structures are drawn in articles, textbooks or web pages about entire phages, not actual structures.) 

Cut-through visualisation of the all-atom model of the T7 bacteriophage in two stages: (left) when it is just touching the outer membrane of a bacterium, and (right) when the core complex is translocated and reconstituted as a trans-envelope channel for genome injection through the outer- and inner membranes of the bacterium. The genome is coloured in yellow. The tail fibre structures (in a compact conformation in the model) are not complete because no experimental structure is available yet for some part. The database entry t7phage @ the gigastructures database will be periodically updated as new structural details emerge in the future.

Teruaki Koto and Tibor Páli (Membrane Biophysics Laboratory) used new, specialised software tools (implemented on the Yasara modelling platform) to build, for the first time, the complete atomic structure of a phage, namely the T7 bacteriophage, from its DNA and protein components, plus membrane bilayer models. Their T7 phage model (illustrated in the figure below) came out most recently in a new open access database of gigastructures. The entry (accession code t7phage) contains ~20 million atoms (excluding hydrogens), and includes 8 protein components, each present in different number of copies, the full genome, as well as two membrane planes. The idea to build the full atomic structure of a phage came to T. Páli about 2 years ago along with questions about the interaction of phage proteins with a membrane bilayer. The effective work took more than a year from gathering the pieces of structural information to completion. A collaboration with YASARA Biosciences GmbH was essential for prompt removal of bugs, coding new features and for providing overall support (K. Ozvoldik is credited for these as being a co-author). The authors acknowledge access to the HUN-REN Cloud (high performance computational infrastructure) and the Bioinformatics Core Facility of the HUN-REN BRC. The T7 phage model is freely available under the CC BY-SA 4.0 (Creative Commons Attribution-ShareAlike 4.0 International) licence. It can be used for, e.g., structure analysis, coarse-grained simulations, all-atom visualisation and for extracting sub-structures. Details of this study will be first presented (as a poster) in the Straub Days of the HUN-REN BRC (in May 20-21, 2025). Next up, the team will: predict the missing part of the fibre protein (as a workaround until an experimental structure become available) and update the model with extended tail fibres; building the full atomic structure of another bacteriophage; and, together with other members of the Molecular Biophysics Research Group, they are to study the molecular biophysics of the interaction of the tail fibre proteins with the membrane, following interesting observations on the T7 phage model. (Requests for custom structure files, scenes, images or animations are welcome – after the first related paper is out.)