AI solution to a 50-year-old science challenge could 'revolutionise' medical research

November 30, 2020

Inside every cell, thousands of different proteins form the machinery that keeps all living things - from humans and plants to microscopic bacteria - alive and well. Almost all diseases, including cancer, dementia and even infectious diseases such as COVID-19, are related to the way these proteins function. Because each protein's function is directly related to its three-dimensional shape, scientists around the world have strived for half a century to find an accurate and fast method to enable them to discover the shape of any protein.

Today (Monday) researchers at the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14) will announce that an artificial intelligence (AI) solution to the challenge has been found.

Building on the work of hundreds of researchers across the globe, an AI program called AlphaFold, created by London-based AI lab DeepMind, has proved capable of determining the shape of many proteins. It has done so to a level of accuracy comparable to that achieved with expensive and time-consuming lab experiments.

CASP14 is organised by Dr John Moult (chair), University of Maryland, USA; Dr Krzysztof Fidelis, UC Davis, USA; Dr Andriy Kryshtafovych, UC Davis, USA; Dr Torsten Schwede, University of Basel and SIB Swiss Institute of Bioinformatics, Switzerland; and Dr Maya Topf, Birkbeck, University of London, UK and CSSB (HPI and UKE) Hamburg, Germany.

Dr Moult said: "Proteins are extremely complicated molecules, and their precise three-dimensional structure is key to the many roles they perform, for example the insulin that regulates sugar levels in our blood and the antibodies that help us fight infections. Even tiny rearrangements of these vital molecules can have catastrophic effects on our health, so one of the most efficient ways to understand disease and find new treatments is to study the proteins involved.

"There are tens of thousands of human proteins and many billions in other species, including bacteria and viruses, but working out the shape of just one requires expensive equipment and can take years.

"Nearly 50 years ago, Christian Anfinsen was awarded a Nobel Prize for showing that it should be possible to determine the shape of proteins based on their sequence of amino acids - the individual building blocks that make up proteins. That's why our community of scientists have been working on the biennial CASP challenge."

Teams taking part in the CASP challenge are given the amino acid sequences for a set of around 100 proteins. While scientists study the proteins in the lab to determine their shape experimentally, about a 100 participating CASP teams from more than 20 countries will try to do the same thing using computers. The results are assessed by independent scientists.

Dr Fidelis said: "The CASP approach has created intense collaboration between researchers working in this field of science and we have seen how it has accelerated scientific developments.

"Since we first ran the challenge back in 1994, we have seen a succession of discoveries, each solving an aspect of this problem, so that computed models of protein structures have become progressively more useful in medical research."

During the latest round of the challenge, DeepMind's AlphaFold program has determined the shape of around two thirds of the proteins with accuracy comparable to laboratory experiments*. AlphaFold's accuracy with most of the other proteins was also high, though not quite at that level.

The CASP organisers say that this success builds on achievements made in previous CASP rounds, both by the DeepMind team and other participants, and that other teams taking part in CASP14 have also produced some highly accurate structures during this round.

Dr Kryshtafovych said: "What AlphaFold has achieved is truly remarkable and today's announcement is a win for DeepMind, but it's also a triumph for team science. The unique and intense way we collaborate with researchers around the world through CASP, and the contributions from many teams of scientists over the years, have brought us to this breakthrough."

He adds: "Being able to investigate the shape of proteins quickly and accurately has the potential to revolutionise life sciences. Now that the problem has been largely solved for single proteins, the way is open for development of new methods for determining the shape of protein complexes - collections of proteins that work together to form much of the machinery of life, and for other applications."

Professor Dame Janet Thornton, Director Emeritus of EMBL's European Bioinformatics Institute (EMBL-EBI), who is not affiliated with CASP or DeepMind, said: "One of biology's biggest mysteries is how proteins fold to create exquisitely unique three-dimensional structures. Every living thing - from the smallest bacteria to plants, animals and humans - is defined and powered by the proteins that help it function at the molecular level.

"So far, this mystery remained unsolved, and determining a single protein structure often required years of experimental effort. It's tremendous to see the triumph of human curiosity, endeavour and intelligence in solving this problem. A better understanding of protein structures and the ability to predict them using a computer means a better understanding of life, evolution and, of course, human health and disease."

Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to