"If I were 30 years younger, I would develop a simulation of the brain"

This is what Nobel laureate in chemistry Martin Karpelos said in the Nobel lecture that described the path to the discovery. Aryeh Warshel spoke about the need for a simple calculation of protein structure and Michael Levitt spoke about the impact of the software he wrote on the world of drug development

"If I were 30 years younger, I would develop a simulation of the brain" said the winner of the Nobel Prize in Chemistry, Martin Karpelos, in the Nobel lecture that described the path to the discovery. He mainly focused on the ways of abstracting the description of dynamic chemical processes so that their description according to quantum mechanics can be used, but the calculation can be done with the help of classical mechanics.

Today, the methods developed by Karpelos, Prof. Arie Varschel and Prof. Mike Levitt allow scientists to simulate many and especially complex proteins such as the ribosome, viruses, whole cells and even the activity of the human brain. In his lecture, Karpelos explained that his part in the process was the simplification of any complicated processes, and that the explanation regarding the implication of this on the understanding of the surface of proteins or any other molecule he leaves to Worschel and Levitt to describe.

But as in any scientific process, here too one must be careful and check that the simulations do indeed represent the real phenomenon in nature: "I always warn my students that even if they discover surprising and new things, to check carefully whether a mistake was made on the way to the discovery."

He left the explanation regarding the projection to Prof. Warshel and Prof. Levitt.

Prof. Aryeh Warshel explained that our body is made up of cells and enzymes that tell it how to behave. And inside the cell there are many junctions on which the same enzymes act, each such junction is a protein, and it is important to know what the shape of each protein is, something that has improved considerably in the last 50 years. Part of the process is understanding how you can learn from the shape of enzymes to understand how it works. "My interest is to understand how complex molecules work." It's like looking at a clock, watching how fast its gears turn, but that doesn't mean we really know how the clock works (Ehud Barak is one of the few who knows how to take a clock apart and put it back together). In enzymes - the crystallography shows us the parts, the spectroscopy of a single molecule shows us how fast it rotates, but I have to know how it works.

He then described how he came to Shneor Lipson's laboratory, even though he did not think of pursuing a scientific career, but thanks to their kibbutzim neighbors Nir David and Sde Nahum. Between the years 1966 and 1969, with the assistance of Mike Levitt, the laboratory dealt with what is known today as CONSISTENCY FORCE FILED and with Mike's help we developed a software that makes it possible to make a mechanical molecule, which made it possible to simplify the molecular model using balls and springs.

Later he described his joint work with Martin Karpelos in his post-doctorate, and what he did later at the Weizmann Institute. We described most of the events in the comprehensive interview we conducted with him about a month ago. "The idea is to focus on the interesting part and represent the rest of the image with fewer pixels."

Towards the end of the lecture, Prof. Warshel explained that today's computing power makes it possible to decipher the action of more and more complex proteins and, in particular, makes it possible to simulate their action for a long time of up to milliseconds. Such a complete simulation even today encounters memory problems (A.B. computer memory), so we developed a model that makes it possible to shorten the duration of the simulation.

The field that interests me today is drug resistance - to know what the next step of a virus or pathogen will be, we can take our knowledge of the drug that the virus defends itself against through mutation, look at the virus's enzymes, which although resist the drug but still must perform their action for the virus to live, and attack this point. For this, it is necessary to carry out extremely complex simulations.

Prof. Michael Levitt spoke about the past and future of computational biology, MULTISCALE MODELING but began by describing the inspiration he received from two Nobel laureates Linus Pauling and co-discoverer of the structure of DNA from Francis Crick. In the sixties, I was inspired by the experimental scientist John Kandro, who published a drawing of myoglobin in 1961 in Scientific American, and Max Perutz, who in 1962 published the structure of hemoglobin on the cover of Scientific American, which at the time was the only newspaper that published scientific illustrations, and was even more important than Science and Nietzsche In the 1965s, David Phillips, the only one in the group who did not receive a Nobel Prize, published the structure of lysozyme in the same journal in XNUMX.

John Kandro, who received a Nobel Prize in 1962, influenced me when in 1964 he presented a science television program on the BBC. I was 16 years old at the time and I came from South Africa, where there was no television at all, in England we had black and white television (or rather black and yellow) and I remember that year I watched the Winter Olympics broadcasts and Kandro's program The Thread of life which presented the field of molecular biology. Kandro is the one who sent me to Israel to work with Aryeh Warshel and Shneor Lipson at the Weizmann Institute, for about a year until a place was found for me in Cambridge.

"Shaneor was really the most important person in the discovery, if you took him out of the process, the discovery would not have happened. He did this through a philosophical idea. At that time in the sixties they realized that the inside of the cell is not just a clot of blood, it is really a machine, just like a watch or a car that needs to know how it works or even like a city - New York for example, Lipson claimed the term "consistent force field" according to him carbon is carbon is carbon but then it was thought that there were different types of carbon (the free carbon is different from the one in carbon dioxide, etc.). In the article Aryeh and Schnior showed that this is especially true for small molecules."

"In the early eighties, I was working on a model of antibodies, and I had a computer program that made it possible to model any type of antibodies. The PDL company issued a patent for them and receives half a billion dollars a year in franchise fees. But there is bad news, firstly, I have no part in it, and secondly, the patent was issued in 1989 and will expire next year." Development began with a Levitt student using his software to model antibodies.

"Our work has been pushed forward thanks to technology. Computers have become 10,000 times more powerful, 10,000 times cheaper and 10,000 times more widely accepted. For calculations to work they need to be simple enough to perform but not too simple to be accurate. You can predict the exact weather for tomorrow but it will take you ten years, especially in a place like Sweden, you need a model that is accurate enough but that runs for two hours."