Issue 1 Article 2

Nobel Intentions: Computer Biology

25/1/20

By:

Lee Zhe Yu, Nathan

Edited:

Wu Yuxuan

Tag:

Biotechnology and Engineering

AI Comes to the Nobels—in bold, emblazoned across the front page, as proudly declared by the Nature’s October headline.

Those who were following the Nobel Prize award ceremony earlier this year would be able to empathise with the disgruntled sentiments raised by some of the researchers quoted in the article. The main source of unhappiness arises from two of the awards, the Nobel Prize in Physics and the Nobel Prize in Chemistry, which seemed to have been awarded for research work done in the field of Computer Science rather than Physics or Chemistry.

Still, why should this matter to us? With the advent of technology, it is almost inevitable that it would revolutionise the way biological research is conducted, with profound ramifications for our daily lives. In this 4-part miniseries, we will delve into various scientific Nobles and the actual work that goes behind them in hopes of finding out just what makes them so impactful.

The Award

The 2024 Nobel Prize in Chemistry was awarded to Dr David Baker, from University of Washington and Howard Hughes Medical Institute, for “computational protein design” alongside Mr Denis Hassabis and Mr John Jumper from Google DeepMind for “protein structure prediction”. This award highlights the growing significance of technology in biological research even up until today.

The Foundations

Every protein is made up of amino acids. Most biological proteins are created from 22 of these amino acids, although over 500 of them exist in nature. In fact, the primary structure of protein is an amino acid chain. As the chain folds due to the chemical interactions between the various ‘residues’, as the individual amino acids are now called, the secondary structure of the protein is formed, with its characteristic local 𝛼-helices and 𝛽-pleated sheets. The protein eventually folds into its 3D structure, also called the tertiary structure of the protein. Each amino acid is like a building block of life; changing a residue in the amino acid chain affects the overall structure of the protein.

Proteins and the world

Proteins are integral to how our world functions. From being structural building blocks of our bodies to acting as vital enzymes in most living things, life would be non-existent without these molecules. With the ability to predict the structures of these proteins quickly, we are now able to understand the chemistry behind the various biological processes that keep our world alive. These technological advancements have the potential to unlock new possibilities and design novel proteins that could have life saving functions on patients.

The Work: Dr David Baker

From the 1980s, protein design had been carried out by testing whether the given amino acid sequence would be able to fit the desired 3D structure of the protein. However, these early efforts were unable to recreate the thermodynamic properties of these proteins, rendering them effectively useless. In 2003, Dr David Baker, along with his research group, designed and experimentally validated the Top7 protein fold, the first protein fold to not be found in nature. This was done by simultaneously optimising for the amino acid sequence and protein structure. An initial perturbation would be created by changing the angle between a few residues in the protein, before changing the side chain of the residues that had experienced an increase in energy and hence had become less stable. Throughout this process, the structure of the protein will be minimised. At the end of 20 rounds, the most stable protein structure and its corresponding amino acid sequence would be selected using a “Monte Carlo optimisation procedure”.

The Work: Google DeepMind

Despite advances in technology, in 2020, the contemporary methods of using physical thermodynamic properties of proteins, as well as the slightly newer method of relying on bioinformatics analysis of the evolutionary history of proteins were still falling short in terms of experimental accuracy. This prompted John Jumper, Director of Google DeepMind, to carry out research on accurate computational approaches to address this gap in research. Using a neural network (its developers had won the 2024 Nobel Prize in Physics), the team at Google DeepMind was able to develop a deep learning algorithm that could “regularly predict protein structures with atomic accuracy even in cases in which no similar structure is known”. The accuracy level of the resulting model, AlphaFold, was able to reach an accuracy level of 0.96 Å checking on 95% of the residues of the protein, which is significantly lower than the next best method available at that time, with an accuracy level of 2.8 Å checking on 95% of the residues of the protein. Their research continues till this day, with AlphaFold2 earning Mr John Jumper and CEO of Google DeepMind Mr David Hassabis their Nobel Prizes in Chemistry, and AlphaFold3 recently completed this year. AlphaFold2, in particular, has been used by more than two million people from 190 countries.

Not just proteins…?

Notwithstanding the importance of proteins, technology’s impact on biological research extends far beyond them. Biochemists of today now run computer simulations, minimizing the need for laboratory work. In the medical research field, the swift rise of novel diseases are being combated with the rapid development of new drugs and treatments to fight them. Even in everyday medical practices, the advancements in medical technology has led to safer techniques employed by doctors to check on our health, whether through Magnetic Resonance Imaging (MRI) or the humble blood pressure monitor. The rapid development of biotechnology has the potential to uplift all areas of biomedical research.

Conclusion

As declared by the New York Times: “[these] discoveries show the potential of advanced technology, including artificial intelligence, to predict the shape of proteins, life’s chemical tools, and to invent new ones”. The new era of technology and Artificial Intelligence has only just begun, and biological research is set to benefit immensely from it. The Nobel Prize of Chemistry 2024 winners, while groundbreaking today, serve as a mere harbinger of what the future entails. Computer science is the future of biological research, and by extension, the world.

Stay tuned for the next part, where we will delve into another biotechnological advancement that has life-changing potential, CRISPR (or Clustered Regularly Interspaced Short Palindromic Repeats) and the Nobel Prize of Chemistry Winners 2020.

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Issue 7 - July 2025

Nobel Intentions: Computer Biology