When chemistry meets computers

Atoms vibrate, electrons jump, and molecules walk from cell to cell. Using computers, scientists at Novozymes can get a better view of the world at molecular scale. We spoke to Martin Karplus, a Nobel Prize Winner who made this possible.

chemistryman700x200​​Chemistry is no longer confined to labs with microscopes, beakers and test tubes. Today, molecules are also studied using computer science to better understand the mysterious ways of chemistry. Molecular simulations in computers make it possible for researchers to try out difficult experiments virtually, before taking them to the lab. That helps them assess whether the experiments will be fruitful or if they need to be changed.  

This ground-breaking method was pioneered by Martin Karplus, Michael Levitt and Arieh Warshel who won the 2013 Nobel Prize in Chemistry for the development of multiscale models for complex chemical systems”.

Professor Martin Karplus, Professor of Chemistry, Emeritus, at Harvard University, recently paid Novozymes a visit to give a lecture on this methodology, which has proven to be one of the tools to transform the way researchers work with enzymes and proteins worldwide. At Novozymes, scientists use the models on a daily basis to understand enzyme functionality, improve existing enzymes and develop new ones.  

Understanding molecules

As living and moving things, molecules are in constant flux, and chemical reactions between them happen at lightning speed. This makes it impossible to map every reaction using traditional methods in chemistry, Martin Karplus explains. The computer models developed by the Nobel Laureates make it possible for scientists to mirror real life experiments in computers to better predict the outcomes. The models are universal, making it possible to simulate any chemical reaction; to understand the nature of diseases, optimize drugs, or design and develop enzymes.

“Studying molecules leads us to understand how cells work, which we can use to understand how living beings work. In fact, studying molecules gives us a fundamental understanding of life itself, because it’s all chemistry,” says Martin Karplus.

Previously, scientists studied molecules on computers using software that was either based on Isaac Newton’s classical model of physics, or quantum physics, each of which has strengths and weaknesses. The first method enables scientists to model large molecules, while it is possible to study chemical reactions in small molecules using the second method. The Nobel Laureates managed to combine the best of both worlds, so that scientist can model large molecules and understand the chemical reactions within them.

“I was interested in understanding how the structure of the molecules makes it possible for them to change their conformations and to carry out their function. So we developed a methodology to study the molecular dynamics using computers,” Professor Karplus says.

Optimizing enzymes

As an innovation-driven company that annually invests 14% of its revenue in R&D, Novoyzmes’ focus is to continuously develop existing products as well as expand the use of biotechnology to develop new solutions. Using computer simulations to understand enzyme dynamics can help us to optimize and improve enzymes.

“With the computer models we can simulate very complex experiments and gain indications of where to look for answers. We can better map enzymes and their chemical composition, and we can simulate how specific enzymes may react to a substrate, such as a stain,” explains Ali Fallah-Araghi, Science Manager at Novozymes.

For example, if we have a protease that demonstrates good washing performance, we can test how it will react to different substrates using a computer, and what may happen to the enzyme when it is exposed to new environments, such as different water quality in various regions.

“This generates data about what goes on inside the enzyme that affects its function, which can lead us to improve existing enzymes and develop new ones,” Ali Fallah-Araghi says. “The data indicates to us where could start working to change the enzymes to make it better. We use the knowledge from the computer to design lab experiments."

Real life experiments

Although chemistry has emerged from the lab and into the realm of computer science, real life experiments are crucial too. After all, computer models that help understand plausible chemical reactions are but an important first step.

“It’s a combination of both lab experiments and computer simulations,” Professor Karplus points out. “Some people say that chemistry is now in cyberspace, but that’s not true. It’s really the interplay between experiments and computations that are necessary to really make advances. So you absolutely need both.” ​​​