Recently, two researchers from Skoltech and McGill University published a review of the promising field of structural proteomics in the journal Chemical Review. This field combines protein chemistry and mass spectrometry and is an advanced analytical method for identifying the chemical composition of a substance based on precise mass. Its ultimate goal is to precisely resolve the structure of the target protein and understand the pathogenesis of diseases like Alzheimer's at the molecular level, so as to predict drug candidate molecules that fight multiple diseases more efficiently and quickly.
The ultimate goal of this method is to accurately resolve the structure of the target protein, understand the pathogenesis of diseases like Alzheimer's at the molecular level, and more efficiently predict the molecular | of drug candidates that fight multiple diseases pxhere
Structural proteomics involves protein structure and interaction and recognition with other proteins, including the binding sites of antibodies or drug molecules on proteins. Today, a series of techniques such as protein molecular surface modification, restrictive proteolysis, hydrogen-deuterium exchange and crosslinking provide important reference data for structural proteomics and more possibilities for assisting the resolution of protein structure.
"In some cases, the binding of two proteins can have serious health effects. This is where this needs to be prevented. For example, this process is common in certain cancers. Study co-author Christoph Borchers, a visiting professor at Skoltech, commented.
In addition to identifying protein interaction sites, another important research direction of structural proteomics is to explore the effects of conformational changes. This refers to the fact that proteins produce different spatial structures only by changing their folded shape without changing their chemical composition. The researchers identified exposed protein interaction sites by studying changes in conformation, which they applied to their interactions with drug molecules or other proteins.
"For example, for some reason, something 'unhealthy' happens in your body," Borchers explains, "and all of a sudden, an interaction happens in your body, and then the proteins start to aggregate and start forming fibrous plaques, which is what Alzheimer's and Parkinson's go through." We need to know what this pathological morphological change looks like, and the structure of the resulting polymer. ”
"Artificial intelligence is of great significance in this area. While it doesn't elaborate on everything, it does help a lot. We can get huge help in understanding conformational changes and their role in neurodegenerative diseases, for example, by combining protein chemistry, molecular models, and artificial intelligence," added Evgeniy Petrotchenko, co-author of the study. He also thinks this could be the biggest application prospect for structural proteomics.
Workflow for determining protein structure through multistructural proteomics-guided discrete molecular dynamics simulations (SP-DMD) | References[1]
"It's true that people's average life expectancy is increasing, but they're still facing cancer, or neurodegenerative diseases, or cardiovascular disease," Borchers added. At the same time, he also pointed out that 90% of new anti-cancer drugs are antibodies, and structural proteomics can also determine the interaction between proteins and antibodies.
"This is a very exciting area," the researchers say, "we've been studying structural proteomics for almost 30 years and have made a lot of progress in developing software packages that can be used to decipher the dynamics of traditional structural analysis tools, such as X-ray scattering, nuclear magnetic resonance or electron microscopy, that can't be deciphered." We have also developed a range of auxiliary methods: crosslinking studies, hydrogen-deuterium exchange, etc. ”
Another feature of structural proteomics is the scale of its operations. Suppose there is a drug, and you need to describe its mechanism of action: Where exactly does it bind to the target protein? (In fact, proteins are the target molecules for the vast majority of drugs.) The function of a protein is determined by its structure, and structural proteomics can determine the structure of not only one protein, but also the structure of multiple proteins that interact at the same time. "This refers to looking at hundreds of protein-protein interactions at once, or even entire protein networks." This is something that no other technique can do," Borchers explains, "and like an orchestra, you have to think about the overall effect." ”
Structural proteomics is one of the areas Skoltech is currently conducting research. In November, the Institute hosted the 10th Structural Proteomics Symposium, an annual online international exchange event organized by Borchers and Petrotchenko and Evgeny Nikolaev of Skoltech.
bibliography
[1] Petrotchenko E V, Borchers C H. Protein Chemistry Combined with Mass Spectrometry for Protein Structure Determination[J]. Chemical Reviews, 2021.
[2] https://www.eurekalert.org/news-releases/941468
Compiler: Zhao Yihe
Edit: Crispy fish
Typography: Yin Ningliu
Research team
Corresponding author Christoph H. Borchers: Graduated from the University of Konstanz, Germany. After postdoctoral training and work at NIEHS/NIH/RTP in North Carolina, USA, he became director of the Duke-University of North Carolina Proteomics Institute and held a faculty position at the University of North Carolina School of Medicine in Chapel Hill, North Carolina. Subsequently, he became Professor in the Department of Biochemistry and Microbiology at the University of Victoria, British Columbia, Canada, and Director of the Center for Genomics BC Proteomics at the University of Victoria, and chaired the Rix BC Biomedical and Environmental Proteomics Leadership Chair. He is currently a professor in the Department of Oncology at the Lady Davis Institute at McGill University, Gerald Bronfman, and director of the Siegel Center for Cancer Proteomics. He is also a visiting professor at the Center for Computational and Data-Intensive Science and Engineering at the Skolkovo Institute of Science and Technology in Moscow, Russia. Dr. Borchers' expertise includes improving, developing, and applying mass spectrometry-based proteomics and metabolomics techniques, with a primary focus on quantitative proteomics and metabolomics techniques for clinical diagnosis. Dr. Borchers is currently a member of the Canadian Academy of Health Sciences and has published more than 300 papers in proteomics and metabolomics.
*Email: [email protected]
First author Evgeniy V. Petrotchenko: Doctor of Medicine from the Second Moscow Medical College in Russia and Doctor of Bioorganic Chemistry from the Institute of Bioorganic Chemistry of the Belarusian National Academy of Sciences. He has conducted postdoctoral research at the National Institutes of Environmental Health Sciences at the National Institutes of Health at the Research Triangle In North Carolina and at the University of North Carolina at Chapel Hill. He has led a structural proteomics group at the University of Victoria. He is currently The Associate Director of the Siegel Center for Cancer Proteomics at the Mrs. Davis Institute at McGill University in Montreal, Canada.
The homepage of the research group https://www.mcgill.ca/translational-research-cancer/christoph-borchers
Thesis information
Published the journal Chemical Reviews
Published December 30, 2021
论文标题Protein Chemistry Combined with Mass Spectrometry for Protein Structure Determination
(DOI:https://doi.org/10.1021/acs.chemrev.1c00302)
If you want to know more about industry and technology venture capital news,
Welcome to pay attention to the fruit shell hard technology