IN SILICO AND MOLECULAR DYNAMIC STUDIES OF NATURAL FLAVONOIDS FOR THEIR INHIBITORY PATTERN AGAINST INTERLEUKIN-6 (1ALU) AND TNF-Α (5MU8) FOR MANAGEMENT OF ULCERATIVE COLITIS

The search for a prospective lead chemical is a time-consuming and complicated procedure that necessitates a lot of money, patience, and labour. Humans have been using phytochemicals, especially secondary metabolites, for this purpose since ancient times, and they are still on the hunt for even source for drug discovery. Natural flavonoids including rhamnetin, eupatorin, and primuletin are involved in the treatment of numerous biological diseases. The research focuses on molecular docking of 10 flavonoid compounds with the Interleukin-6 (1ALU) and TNF-α (5MU8) to assess the binding affinity at the binding location with the highest binding affinity. The flavonoid-protein complex with the highest binding affinity and interactions was studied using molecular dynamics modelling. With the Interleukin-6 (1ALU) and TNF-α (5MU8), the flavonoid naringin had the lowermost binding energy of 9.8 Kcal/mol. It took 20 nanoseconds to complete and yielded satisfactory results. The rhamnetin, eupatorin, and primuletin residues are more successful at maintaining flavonoid stability against Interleukin-6 (1ALU) and TNF-α (5MU8), according to the overall results of our simulation. These expected results will serve as a starting point for more investigation into the significance of their drug-likeliness properties in the management of ulcerative colitis.

Four propellers submarine drone modelling in a real environment

<span lang="EN-US">In order to reduce the hydrodynamic dampers and mechanical elements as rudders, we have in our previous publications proposed our architectural solution of an ROV with only four thrusters without rudders or diving bars. In the results we have justified the choice of the arrangement of the thrusters. Also, we have started the kinematic and dynamic studies of the marine robot and we have especially demonstrated by using the mathematical model under MATLAB in the last publication, that this ROV can move in a perfect environment without gravity or hydrodynamic dampers. In this article, we will study the behavior of this marine vehicle in a real environment with gravity and hydrodynamic dampers and we will view if this architectural solution can really allow the ROV to move and execute the given directional instructions.</span>

Exploring the Role of L10 Loop in New Delhi Metallo-β-lactamase (NDM-1): Kinetic and Dynamic Studies

Four NDM-1 mutants (L218T, L221T, L269H and L221T/Y229W) were generated in order to investigate the role of leucines positioned in L10 loop. A detailed kinetic analysis stated that these amino acid substitutions modified the hydrolytic profile of NDM-1 against some β-lactams. Significant reduction of kcat values of L218T and L221T for carbapenems, cefazolin, cefoxitin and cefepime was observed. The stability of the NDM-1 and its mutants was explored by thermofluor assay in real-time PCR. The determination of TmB and TmD demonstrated that NDM-1 and L218T were the most stable enzymes. Molecular dynamic studies were performed to justify the differences observed in the kinetic behavior of the mutants. In particular, L218T fluctuated more than NDM-1 in L10, whereas L221T would seem to cause a drift between residues 75 and 125. L221T/Y229W double mutant exhibited a decrease in the flexibility with respect to L221T, explaining enzyme activity improvement towards some β-lactams. Distances between Zn1-Zn2 and Zn1-OH- or Zn2-OH- remained unaffected in all systems analysed. Significant changes were found between Zn1/Zn2 and first sphere coordination residues.