4.24.24
Fabio Bergamin
A new computer process developed by chemists at ETH Zurich makes it possible to generate active pharmaceutical ingredients quickly and easily based on a protein’s three-dimensional surface. The new process could revolutionize drug research.
A new generative AI develops molecules from scratch in such a way that they precisely match the protein they are to interact with. (Visualizations: ETH Zurich / Gisbert Schneider)
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In brief
-Researchers at ETH Zurich have created a generative artificial intelligence (AI) for developing drug molecules based on the three-dimensional surface of proteins with which the molecules are to interact.
-The new computer process ensures right from the start that the molecules can also be chemically synthesized.
-The scientists have made their new software available to researchers worldwide, who can now use the method for their own projects.
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“It’s a real breakthrough for drug discovery,” says Gisbert Schneider, Professor at ETH Zurich’s Department of Chemistry and Applied Biosciences. Together with his former doctoral student Kenneth Atz, he has developed an algorithm that uses artificial intelligence (AI) to design new active pharmaceutical ingredients. For any protein with a known three-dimensional shape, the algorithm generates the blueprints for potential drug molecules that increase or inhibit the activity of the protein. Chemists can then synthesize and test these molecules in the laboratory.
All the algorithm needs is a protein’s three-dimensional surface structure. Based on that, it designs molecules that bind specifically to the protein according to the lock-and-key principle so they can interact with it.
Excluding side effects from the outset
The new method builds on the decades-long efforts of chemists to elucidate the three-dimensional structure of proteins and to use computers to search for suitable potential drug molecules. Until now, this has often involved laborious manual work, and in many cases the search yielded molecules that were very difficult or impossible to synthesize. If researchers used AI in this process at all in recent years, it was primarily to improve existing molecules.
Now, without human intervention, a generative AI is able to develop drug molecules from scratch that match a protein structure. This groundbreaking new process ensures right from the start that the molecules can be chemically synthesized. In addition, the algorithm suggests only molecules that interact with the specified protein at the desired location and hardly at all with any other proteins. “This means that when designing a drug molecule, we can be sure that it has as few side effects as possible,” Atz says.
To create the algorithm, the scientists trained an AI model with information from hundreds of thousands of known interactions between chemical molecules and the corresponding three-dimensional protein structures.
Successful tests with industry
Together with researchers from the pharmaceutical company Roche and other cooperation partners, the ETH team tested the new process and demonstrated what it is capable of. The scientists searched for molecules that interact with proteins in the PPAR class – proteins that regulate sugar and fatty acid metabolism in the body. Several diabetes drugs used today increase the activity of PPARs, which causes the cells to absorb more sugar from the blood and the blood sugar level to fall.
Straightaway the AI designed new molecules that also increase the activity of PPARs, like the drugs currently available, but without a lengthy discovery process. After the ETH researchers had produced these molecules in the lab, colleagues at Roche subjected them to a variety of tests. These showed that the new substances are indeed stable and non-toxic right from the start.
The researchers aren’t now pursuing these molecules any further with a view to bringing drugs based on them to the market. Instead, the purpose of the molecules was to subject the new AI process to an initial rigorous test. Schneider says, however, that the algorithm is already being used for similar studies at ETH Zurich and in industry. One of these is a project with the Children’s Hospital Zurich for the treatment of medulloblastomas, the most common malignant brain tumors in children. Moreover, the researchers have published the algorithm and its software so that researchers worldwide can now use them for their own projects.
“Our work has made the world of proteins accessible for generative AI in drug research,” Schneider says. “The new algorithm has enormous potential.” This is especially true for all medically relevant proteins in the human body that don’t interact with any known chemical compounds.
Science paper:
Nature Communications
See the science paper for instructive material with images.
See the full article here .
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The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH) is a public research university in the city of Zürich, Switzerland. Founded by the Swiss Federal Government in 1854 with the stated mission to educate engineers and scientists, the school focuses exclusively on science, technology, engineering and mathematics. Like its sister institution The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne](CH) , it is part of The Swiss Federal Institutes of Technology Domain (ETH Domain)) , part of the The Swiss Federal Department of Economic Affairs, Education and Research [EAER][Eidgenössisches Departement für Wirtschaft, Bildung und Forschung] [Département fédéral de l’économie, de la formation et de la recherche] (CH).
The university is an attractive destination for international students thanks to low tuition fees of 809 ₣ per semester, PhD and graduate salaries that are amongst the world’s highest, and a world-class reputation in academia and industry. There are currently students from over 120 countries, many of which are pursuing doctoral degrees. In the QS World University Rankings ETH Zürich is ranked very highly in the world and very highly by the Times Higher Education World Rankings. In the QS World University Rankings by subject it is ranked very highly in the world for engineering and technology, earth & marine science.
Nobel laureates, Fields Medalists, Pritzker Prize winners, and Turing Award winners have been affiliated with the Institute, including Albert Einstein. Other notable alumni include John von Neumann and Santiago Calatrava. It is a founding member of the IDEA League and the International Alliance of Research Universities (IARU) and a member of the CESAER network.
ETH Zürich was founded on 7 February 1854 by the Swiss Confederation and began giving its first lectures on 16 October 1855 as a polytechnic institute (eidgenössische polytechnische schule) at various sites throughout the city of Zurich. It was initially composed of six faculties: architecture, civil engineering, mechanical engineering, chemistry, forestry, and an integrated department for the fields of mathematics, natural sciences, literature, and social and political sciences.
It is locally still known as Polytechnikum, or simply as Poly, derived from the original name eidgenössische polytechnische schule, which translates to “federal polytechnic school”.
ETH Zürich is a federal institute (i.e., under direct administration by the Swiss government), whereas The University of Zürich [Universität Zürich ] (CH) is a cantonal institution. The decision for a new federal university was heavily disputed at the time; the liberals pressed for a “federal university”, while the conservative forces wanted all universities to remain under cantonal control, worried that the liberals would gain more political power than they already had. In the beginning, both universities were co-located in the buildings of the University of Zürich.
From 1905 to 1908, under the presidency of Jérôme Franel, the course program of ETH Zürich was restructured to that of a real university and ETH Zürich was granted the right to award doctorates. In 1909 the first doctorates were awarded. In 1911, it was given its current name, Eidgenössische Technische Hochschule. In 1924, another reorganization structured the university in 12 departments. However, it now has 16 departments.
ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École polytechnique fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.
Reputation and ranking
ETH Zürich is ranked among the top universities in the world. Typically, popular rankings place the institution as one of the best universities in continental Europe and ETH Zürich is consistently ranked among the top universities in Europe, and among the best universities of the world.
Historically, ETH Zürich has achieved its reputation particularly in the fields of chemistry, mathematics and physics. Nobel laureates are associated with ETH Zürich, the most recent of whom is Richard F. Heck, awarded the Nobel Prize in chemistry in 2010. Albert Einstein is perhaps its most famous alumnus.
The QS World University Rankings placed ETH Zürich very high in the world. ETH Zürich has ranked very highly in the world in Engineering, Science and Technology, just behind The Massachusetts Institute of Technology, Stanford University and The University of Cambridge (UK). ETH Zürich also ranked very highly in the world in Natural Sciences, and in Earth & Marine Sciences.
The Times Higher Education World University Rankings has ranked ETH Zürich very highly in the world in the field of Engineering & Technology, just behind
The Massachusetts Institute of Technology, Stanford University, The California Institute of Technology, Princeton University, The University of Cambridge (UK),
Imperial College London (UK) and
The University of Oxford (UK).
In a comparison of Swiss universities by swissUP Ranking and in rankings published by CHE comparing the universities of German-speaking countries, ETH Zürich traditionally is ranked very highly in natural sciences, computer science and engineering sciences.
In the survey CHE Excellence Ranking on the quality of Western European graduate school programs in the fields of biology, chemistry, physics and mathematics, ETH Zürich was assessed as one of the institutions to have excellent programs in all the considered fields, the other two being Imperial College London (UK) and the University of Cambridge (UK), respectively.
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