 Maybe we will proceed with the presentation, the next coming presentation of Dr. Fatma Gil-Mustan-Buresova from the Faculty of Chemistry and Pharmacists of University, and she will share further with us molecular dynamic simulations of phenulfibrata solubilization into bile salt and fatty acid mitzvahs. So, please, Prof. Mustan-Buresova. Hello. Thank you for the introduction. I'll present a brief introduction about our study and I'll define our aim of the study and present the use of computational protocol and the molecular models. And I'll explain the obtained results about the pure bile salt micelles, mixed micelles with fatty acids and solidification of phenulfibrates and I'll finish with the main. So, the bile salts are the polyhydroxy steroid acids, which are the phobic steroid parts illustrated here. And the part containing two or three hydroxy groups and some pedophilic tails, which can be conjugated by glycine or acid there, their main role is in the gastrointestinal tract of the human. And that is why it is important to see their aggregation behavior because their aggregates can stabilize hydrophobic molecules from the gastrointestinal tract and also some hydrophobic drugs. So, we know that the conventional sympathons, which are contained hydrophilic fats and hydrophobic long form of spherical or cylindrical micelles or lamellar phases depending on their concentration in the solutions. But due to the specific chemical structure of the bath salts, they form more different micelles called primary and secondary mice. The primary micelles are characterized with aggregation numbers below 10 and the main penforces that stabilize them are the hydrophobic interactions. And by hydrogene bonding, the primary for secondary mice with aggregation number above 10, they also can form some dyspolytic micelles or helical micelles at some specific conditions. So, in the literature, there are a lot of experimental results of their aggregates and found they are very small and also some molecular dynamics simulations, but for them are at very high concentration of bath salts, but their concentration in the gastrointestinal tract is very low. And that is why we decided to study their behavior at conditions close to the conditions in the gastrointestinal tract in the months as by monitoring the kinetics of aggregation of six bio salts and analyze twin molecular forces acting between the most stable aggregates and also to define their shape and size. We used six different molecules, so folate and deoxyfolate, folate is the derivatives with three hydroxy groups, oxyfolate is with two hydroxy groups in the hydrophilic tract, and they are glycine and sourine-conjugated derivatives. So, we used two mystic molecular dynamics simulations in the monoclonal sample with four fields, number nine for describing the bio-sculptor molecules and tip-tip for water molecules. We placed random molecules in periodic box with sizes in three directions, 11 nanometers, and we run the production around 150 nanoseconds. As a first step, we analyzed the aggregation process during the simulation, and here the maximum poster size. So, as a function of the simulation, we presented four three hydroxy and two hydroxy derivatives, and here you can see that the process is hierarchical and the fastest for deoxyfolate here and the biggest aggregates are formed by glycine-conjugated derivatives, and they are conjugated and non-conjugated derivatives for stable pentamels. We compared the obtained aggregation with the experiment determined at similar conditions, and we found a very good agreement with the experimental data molecules to compute three hydroxy groups in the hydrophilic part, but there is a big difference between our data and the experimental data about the aggregation of the deoxy derivatives. It is due to the fact that in the observed formation of secondary micelles, the entities dispute that three hydroxy derivatives are stable primary micelles, deoxyfolate, but deoxy derivatives are secondary micelles, but in our case, we have only eight molecules in the periodic box, but we cannot observe formation of secondary micelles. So, this is the illustration of these stable aggregates. Here you can see there is no orientational ordering of the molecules within the aggregates, and actually they are very dynamic, and they are positioned in the aggregates, and it can allow them to solidify very easily some hydropobical molecules in their vicinity. So, we also studied the interaction between these molecules. We analyzed the number of contacts between the molecules here in these stable aggregates. Here the population of the number of minimum distances between the molecules in the stable aggregates are presented for the tree and the deoxy derivatives, and here you can see that these distances are very short-ended here. It means that no water molecules immersed inside the aggregates and the area between the molecules is completely hydrophobic. It can come from these pictures where the green parts are the hydrophobic parts and the red ones are the molecules. And from this study, from the first part of the study, we include small primary micelles that are formed in all systems that load biosolids concentration, with a radius of about one nanometer. We calculated it, analyzing the radius of duration, and also the shape for all of them are the formed ellipsoid or non-ordered. Also, aggregates are formed by glycine derivatives, while stored conjugated and non-conjugated biosolids form stable pentameters. The driving forces for aggregation are hydrophobic interactions between the sterile trees and the core of the micelles are entirely hydrophobic and does not tolerate inclusion of water molecules. This fact and the fact that they're intensive dynamic of the molecules within the aggregates can explain their capacity to hydrophobic molecules. In our department, we did an experiment with tower deoxiculate perforate to study their solubilization capacity by using a phenophybrate drug molecule, which is a hydrophobic molecule. And it is studied the solubilization of the drug molecule in the solutions of only a biosolid and the solutions of biosolids mixed with fatty acids. And here, amount of solubilized phenophybrates as a function of saturated fatty acids chain length is shown, and it can be seen that there is a maximum at C14. But when unsaturated fatty acids are used, solubilized phenophybrates increase with a significant and based on this experimental data, we defined our aims for the second part of the study by to monitor the micelle formation of tower deoxiculate without and without fatty acids and try to determine the amount of the solubilized drug in the micelle. So we studied only tower deoxiculate as a biofoss because the experiments are performed to use phenophybrates as a drug molecule. It is frequently encountered in lipid-based formulations in the world monitor. As fatty acids we studied the myri-state, stearate and oreate, all of them are salt. So a new computational protocol is the same as the previous study with this difference that in the 100 molecules of tower deoxiculate, 100 molecules of fatty acids when they present and 40 molecules of the length of the production run. In this case, it's 300 nanoseconds and the periodic box is larger. This is the initial configuration of the systems with only tower deoxiculate, water molecules and the cation electrolytes. We constructed four different initial configurations in order to check the reproducibility of the applications in respect to the aggregation processes. And here the average cluster size and the maximum cluster size is a function of simulation for different simulations are presented. And here you can see that we have very good reproducibility in respect to the average size. We entered the reproducibility for the maximum cluster size is also acceptable. From these simulations we determined the average cluster size after 300 nanoseconds because we have that here the equilibrium state is reached. And we compared this cluster size with experimental data and we obtained a very good agreement. And we can say that our protocol is very good to reduce experimental behavior of these molecules. Next step was the addition of fatty acids here. The initial configuration of the system with deoxiculate and cation electrolytes are shown. In fact, that in the experiments the fatty acids are added in the solution of the deoxiculate where the micelles are formed already. That is why the simulation we tried to mimic the experimental procedure and that is why the fatty acids molecules are randomly placed inside the deoxiculate micelles. Here the average cluster size is a function of simulation time for the systems with the mirror state and the electrolyte. The picture is similar with the stare rate. In all cases we have formation of micelles between the deoxiculate and the fatty acid which is not clear from the experiment actually. We can afford that yes in the experiment we have mixed micelles which fertilize the drug. The table will summarize the data about the composition of all obtained aggregates. These are molecules in all formed aggregates in the systems. And here you can see that in the case of fatty acids we are pure of fatty acids aggregates in addition to the mixed aggregates. And in these mixed aggregates the ratio between the deoxiculate and the fatty acid varies in wide range that the content of these aggregates are very different. And it will be interesting to see in which aggregates the molecules of the drugs will polypilize. And the next step was to add a drug molecule in this module systems. So due to the fact that the phenol fibrate is non-polybolic and in the experiment it is a crystal in the solution of the polypilates together with the fatty acids. And that is why we formed such aggregates from the phenol fibrate and placed it randomly inside the periodic boxes with the deoxiculate micelles and fatty acid molecules run on the 300 nanoseconds of simulations. In all cases, all the molecules in the initial aggregates of phenol fibrate remain in the same aggregates. There is no separation of phenol fibrate molecules from the case. But there is some incorporation of basalt and fatty acid molecules in this. And this is the illustration after 300 nanoseconds of simulations. Here you can see that in pure c-polyoxiculate, the phenol fibrate aggregates surrounded from by the molecules of the polyoxiculate. But it's of the meristate and OLED. They are immersed between the phenol fibrate molecules. And here there are polyoxiculate molecules between the water medium and the aggregates where all the molecules are inside between the phenol fibrate molecules. In case after it, it's a little bit different. In this case,