A new, powerful and publicly available web resource known as Aquaria – providing quick and extensive insight into the 3D structure of proteins – is set to help life scientists better understand diseases and develop new medicines.
If you’re a regular at the gym or an early morning boot-camp fanatic, it’s possible that the first thing you picture when you think of protein is the powder you use to make your post-workout recovery shake.
But when scientists discuss protein, they’re talking about the many thousands of molecules that act as the essential building blocks of life as we know it. Because proteins are so important to constructing life, researchers need a way to visualise the 3D structures of proteins and the exact ways in which they fit together, so as to fully understand their functions – in our bodies and elsewhere in nature.
With this in mind, an international team of programmers and bioinformaticians (think biology, computer science and maths mixed together) has created a new web-based tool named Aquaria that can create unprecedented 3D representations of protein structures, as reported recently in the journal Nature Methods.
“In the past, the search for protein structures was very tedious and required expert knowledge. In Aquaria, all data are already processed,” explains Andrea Schafferhans from Technische Universität München (TUM) in Germany. Schafferhans co-developed Aquaria along with researchers led by Seán O’Donoghue from the Australian national science agency CSIRO and the Garvan Institute of Medical Research, Australia.
46 million computer models
Aquaria calculates the structure of most proteins and is based on the Protein Data Bank, an online resource that houses more than 100,000 known protein structures.
“The Protein Data Bank is a fantastic resource containing a wealth of detail about the molecular processes of life, but we were aware that few biologists take full advantage of it,” says O’Donoghue.
“So we created Aquaria to make this valuable information more accessible and easier to use for discovery purposes.”
Freely and publicly accessible, Aquaria will be useful to a broad range of life scientists, from medical researchers to those studying agriculture, biosecurity, ecology and nutrition. It can help them streamline their discovery process and gain new insight into protein structures.
“What we’ve done is to layer in a lot of extra useful information. For example, we’ve added protein sequences that don’t yet have a structure, but are similar to something in the Protein Data Bank,” says O’Donoghue.
“That meant we first had to find all these similarities. So we took over 500,000 protein sequences and compared every one of them with the 100,000 known protein structures – and that has given us around 46 million computer models.”
This is twice as many models as all other similar resources combined. With a fast, easy-to-use interface, Aquaria is set to help researchers navigate a brave new world of possibility.
Enter the name of your favourite protein
All a scientist needs to do is enter the name of their favourite protein into the search field of the online program, which then shows the actual 3D structure or various possible structures of the protein. In addition, it shows all kinds of other information – such as genetic differences between individuals, mapped onto 3D structures.
For example, scientists can visualise how a small change in the DNA code can change an individual amino acid and thus alter a protein’s structure – and, as a result, its function in the body.
“In this way, disease-triggering sequence variants can be viewed in their environments,” explains TUM’s Burkhard Rost, who was part of the Aquaria team. “This insight could be decisive in the development of medications or might facilitate understanding the effects of the variants.”
Further functions in Aquaria are planned for the future, according to Schafferhans. “We are looking at investigating interactions between small molecules like hormones and medications in more detail and making them searchable,” she says.
The project was funded by the Alexander von Humboldt Foundation in Germany. Aquaria is hosted with support of a grant from Amazon Web Services.