Nobel Prize in Chemistry – comment by prof. Piotr Stefanowicz, chemist from the University of Wrocław

The accomplishments of this year’s Nobel Prize laureates in chemistry allow to reliably predict proteins’ structures based on their amino acid sequences, that is, the gene sequences that code for a protein. Protein folding has been a challenge for chemists for the last 50 years, and the problem has finally been solved, comments prof. Piotr Stefanowicz from the Department of Organic Chemistry at the Faculty of Chemistry of the University of Wrocław.

Ever since the discovery of proteins’ spatial structure, chemists and biochemists have been wondering about the connection between the sequence of amino acids (called the protein’s primary structure) and the three-dimensional structure of a protein. The discovery of that connection is of great practical importance, as it is the three-dimensional structure that determines a protein’s biological function and how it binds with other molecules. Knowledge of that structure enables the creation of new medications and vaccines, as well as allows a deeper understanding of how proteins interact with one another within a cell.

Moreover, finding that connection has become even more crucial in the 21^st century, as learning about the genomes of numerous organisms has indirectly allowed us to access the sequences of the proteins they can create.

A couple of days ago, the Nobel Prize in Chemistry was awarded for a groundbreaking achievement in predicting protein structures. Half of the award was granted to David Baker. Initially, Baker developed the Rosetta program, which aided in the modeling of proteins’ spatial structures based on their sequences. Later, he began using this tool to design proteins that do not exist in nature. He sought an amino acid sequence that could create the spatial structure of a specific protein. In this way, he created an interesting protein called Top7. Previously, to create proteins that would, for instance, exhibit enzymatic activity, researchers would use already existing structures, making gradual modifications.

An example of a practical application of Baker’s method is the design of a protein molecule, which can selectively bind fentanyl. Potentially, it could be used to detect that substance in the environment.

Proteins designed by Baker’s team were then produced with the use of biotechnology. It turned out that the produced proteins, to a high degree, corresponded with the designed structures.

It should be noticed, however, that proteins can vary surprisingly widely in their sequences.

For example, a molecule with 100 amino acids (the lowest amount of amino acids in existing proteins) can have 20100 variants. Those unbelievably high numbers exceed the number of all the atoms in the cosmos. In the Earth’s biosphere, there are probably a couple of hundred million proteins (approximately 109 million). These two numbers illustrate the limited number of proteins we can discover through experiments and indicate the vast number still yet to be found.

The second half of the award was granted to Demis Hassabis and John Jumper, who developed an effective computer program, which allows to determine proteins’ structures based on their sequences.

Interestingly, Hassabis has never researched subjects connected with chemistry or biochemistry before. As a talented chess player, he worked on utilizing artificial intelligence to further improve algorithms, which could compete with humans in board games.

Hassabis later employed his previously developed methods for predicting protein structures, which quickly proved to be successful, as his program AlphaFold enabled him to accurately predict 60% of the structures, while competing programs were only 40% effective. His cooperation with John Jumper led to modifications of his program and the creation of its new version, AlphaFold2. The protein structures designed by AlphaFold2 turned out to be almost entirely identical to the data from the crystallographic database.

The accomplishments of this year’s Nobel Prize laureates in chemistry allow to reliably predict proteins’ structures based on their amino acid sequences, that is, the gene sequences that code for a protein. Protein folding has been a challenge for chemists for the last 50 years, and now it has finally been solved, comments prof. Piotr Stefanowicz from the Department of Organic Chemistry at the Faculty of Chemistry of the University of Wrocław.

prof. Piotr Stefanowicz from the Department of Organic Chemistry at the Faculty of Chemistry of the University of Wrocław, leader of the Peptide Engineering Research Group https://chem.uwr.edu.pl/wydzial/struktura-wydzialu/zespoly-badawcze/zb-3-zespol-inzynierii-peptydow/

Written by: Katarzyna Górowicz-Maćkiewicz

Date of publication: 11.10.2024
Added by: A.M.

Translated by Marta Kawik (student of English Studies at the University of Wrocław) as part of the translation practice.