Physicists develop methods of predictive modeling in medicine
Scientists of Far Eastern Federal University (FEFU) have designed the way WW domain of the FBP28 protein acts and came up with a greater awareness of how proteins work, and what proteins' failures provoke various diseases, including neurodegenerative and oncology. To do so, physicists applied the solitons theory, which usually is used to modeling nonlinear phenomena - from the structure of elementary particles to tsunamis. A related article appears in The Journal of Physical Chemistry.
As opposed to ordinary waves, solitons or nonlinear waves hold on their shape when propagate. That, for example, determines the destructive power of a tsunami. FEFU physicists suggest that the stability of three-dimensional protein molecules are of the same nature as nonlinear waves are, which means that one can describe their structure as a set of solitons.
Teamed up with colleagues from Cornell and Stockholm Universities, scientists have studied the WW domain of the FBP28 protein to find out the reasons this domain works correctly or incorrectly.
The researchers have spotted in what way the replacement of some amino acids reshapes the entire structure of the protein, and, most importantly, the effect made by change of specific amino acids in certain links of the molecular chains. For example, if the WW-domain has an irregular structure or is unformed, this can lead to the uncontrolled growth of organs.
"One of the fundamental challenges for us to deal with is to comprehend which exact mutations correspond to incorrect folding of proteins and what purposeful changes in the proteins to be made to fix these errors. If we answer these questions, we will be capable of treating not only neurodegenerative diseases but also type 2 diabetes, oncology, and congenital disorders associated with damage at the genetic level," says Alexander Molochkov, Head of the Laboratory of Physics of Living Matter at the FEFU School of Biomedicine.
The difficulty is that the outcome of the protein mutation is rarely predictable. Any changes in any amino acids are not in direct or any obvious way responsible for the whole protein structure reshaping. To approach that, one has to calculate protein changes via molecular dynamics using super-productive computers. Yet, the method does not work if the protein contains more than a couple of tens of amino acids since there is no computational power, which is enough for such calculations. The solution scientists come up with is to model a protein using the theory of solitons, which at first glimpse is alien for structural biology and medicine.
Applying the solitons theory FEFU scientists hope to develop methods for predictive modeling of protein behavior. Success in that will greatly affect pharmacology and help to learn more about the way many cellular mechanisms and viruses work.
Scientists also want to master methods of artificial protein folding and unfolding (ways how protein molecular chains bend). Using that in the future, one will make a group of proteins folding in a certain way to destroy a virus. This is an example of the control of enveloped viruses, which include both Ebola and AIDS, and the notorious SARS-CoV-2 caused the COVID-19 pandemic.
The knowledge about proteins folding/unfolding will help to launch controlled mutations in the human body to cure congenital diseases caused by the malfunction of one of the proteins always associated with changes in DNA.
Failures in the molecular chains of protein molecules bring about various diseases, including oncology and neurodegenerative diseases - Alzheimer, Parkinson, Huntington, Creutzfelt-Jacob disease or infectious dementia syndrome, when proteins cause dementia, a persistent decrease in cognitive activity with the loss of previously acquired skills.
At the next stage of the study, scientists plan to analyze amyloid proteins, which mutations lead to the development of Alzheimer's disease
In 2020, the FEFU Laboratory of Physics of Living Matter headed by Alexander Molochkov to be reorganized into the Pacific Quantum Center, where the fundamental principles of promising quantum materials, medicine, and pharmacology will be investigated via particle physics methods. The work will include the development of new antiviral drugs.
More information:
pubs.acs.org/doi/10.1021/acs.jpcb.0c00628
DOI 10.1021/acs.jpcb.0c00628
Provided by Far Eastern Federal University
