Events

Seminar of Physics at Wrocław University of Technology

Physics and biomedical methods for molecular studies regarding contacts in the protein world

prof. dr hab. inż. Małgorzata Kotulska

Katedra Inżynierii Biomedycznej, Wydział Podstawowych Problemów Techniki, Politechnika Wrocławska

Abstract:

Experimental study of a molecular structure is expensive, time consuming and not always feasible. The difficulty with such experiments resulted in a great disproportion between the numbers of protein sequences and their structures. Bioinformatics modeling can help to predict the molecular structure, based on a protein sequence. Various computational methods, developed throughout the years, used different approaches, also including machine learning. However, the quality of results was rather mediocre and not satisfactory. Unexpectedly a niche approach only aiming at modeling the intramolecular contacts distribution, using physics methods and a clever molecular idea, finally led to a great breakthrough and sensational release of the method capable of fast modeling protein structures with the qualities comparable to experiments – AlphaFold.
Furthermore, a physiologically irregular distribution of intramolecular contacts may assume a very regular and dense zipper-like pattern. Such proteins, called amyloids, are unusually durable in terms of their mechanical stability and not susceptible to proteolytic enzymes. They are very interesting for material sciences and used by some organisms for functional roles. However, in most biological cases they mark an onset of a severe disease, such as Alzheimer’s, Parkinson’s, and many others. The question to address is whether the onset of such unhealthy contacts is predictable and whether we can control the process.
Finally, intermolecular contacts between proteins constitute an essential layer in multi-omics approach to biomedical knowledge. Protein-protein interaction datasets, which can be represented and analyzed as networks, give insight into molecular pathways, help to uncover novel drug targets or potentially negative consequences of interactions between human physiological proteins and metabolic products of bacteria inhabiting our organism. This includes inter-species contacts of amyloid proteins from humans and bacteria. Nevertheless, the data that constitute such data sets are frequently incomplete, error-prone and strongly biased by scientific trends. Unfortunately, such shortcomings are not easily detectable.
In the talk, I will lead you through our research related to contacts of proteins, starting from pre-AlphaFold era and modern approaches, through methods devoted to amyloid proteins, and finally presenting analytical methods for evaluating the quality of data in protein-protein interaction networks.