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Soutenance d'HDR Sergey Samsonov, CEPR, Tours

Sergey Samsonov will defend his HDR thesis on the 11th of December 2018 in Tours. His work addresses various scientific challenges in the field of computational analysis of protein-GAG interactions and contributes to the better fundamental understanding of those systems, which potentially could serve to guide the design of new methods for tissue regeneration and healing.
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 Sergey Samsonov

 

Dr. Samsonov obtained his Master Degree in Biophysics at the State Polytechnical University of Saint-Petersburg and since then he has been working with different aspects of modeling protein interactions. In particular, in his PhD carried out at Dresden University of Technology, he computationally investigated the role of solvent in protein-protein interfaces and studied the properties of non-natural fluorinated amino acids. In his second PhD, obtained at Saint-Petersburg State University, he proposed a molecular model of CTR1, a putative copper I transmembrane transporter. After obtaining his PhD, he has been focusing on proteinglycosaminoglycan (GAG) molecular systems working within an interdisciplinary and highly collaborative environment within TRR67 DFG project at Dresden University of Technology. From May 2017, he is an independent project leader at the University of Gdańsk, where he continued and broadened his GAG-related research. The presented HDR Thesis of Dr. Samsonov is devoted to computational analysis of protein-GAG interactions. Protein-GAG interactions are crucial for many biologically highly relevant processes such as cell signaling via interactions with their protein targets as chemokines, growth factors in the extracellular matrix. The values of understanding these interactions could be hardly overestimated for the design of new therapies in the field of regenerative medicine. Due to the difficulties in experimental analysis of these systems, computational studies on protein-GAG interactions substantially gained in importance in the recent decade due to the increase in the available computational power. However, GAGs also represent very challenging molecules for computational approaches due to their flexibility, periodicity, anionic nature and the lack of specific computational
techniques developed for GAG containing systems. Therefore, the scientific goals of Dr. Samsonov consisted of the development of the specific computational tools based on molecular docking and molecular dynamic approaches and the application of these tools to particular protein-GAG systems in order to complement, explain and guide the experimental work of collaboration partners. In these terms, he had the following main achievements reflected in three separate sections of the presented HDR Thesis:
1. The experimentally available in the Protein Data Bank protein-GAG complexes were analyzed in terms of their dynamic, energetic and structural properties.

2. A computational pipeline to predict the structures of protein-GAG complexes and to characterize them computationally was established so that the results obtained using this pipeline could be directly compared to the experiments and suggest the biologically relevant molecular mechanisms mediated by these interactions. In particular, several GAG interaction partners as IL-8, SDF-1, BMP-2, cystein cathepsin proteases, osteoprogerin, sclerostin, TGF-β1, TIMP-3 were characterized in terms of their interactions with GAGs. The dependence of protein-GAG interactions on GAG net sulfation, type and length was observed. Based on these results, it could be summarized that GAGs can be involved in the interactions of their protein targets with their receptors by different
mechanisms: directly blocking receptor binding sites; shifting probability distributions in conformational ensemble of the protein influencing, in turn, the probability of binding the receptor; repulsing receptors via long-ranged electrostatic interactions; supporting interactions via formation of sandwich structures; predetermining the sequence of binding events in protein tertiary complexes.

3. Docking approaches and molecular dynamics based protocols are developed and designed in order to deal with protein-GAG systems specifically and more effectively than it has been possible using standard tools with default parameters so far. This work, in particular, included the analysis of the solvent role in protein-GAG interfaces, conformational analysis of GAG molecules as well as their monosaccharide components, prediction of GAG binding sites, development of a molecular dynamics-based docking approach taking into account both receptor and ligand flexibility as well as explicit solvent, a coarse-grained model of GAGs. The reported in this section work focused on
fundamental properties of protein-GAG systems, while the development of systems-specific methodology contributes to broadening our knowledge of protein-GAG molecular recognition and could be useful to steer a choice of the strategies to be applied in theoretical studies of these systems and for the complementation with the experiments.