Cerebral Ischemia is a neural disease which causes dying of a number of people every year. The disease usually exposures since stopping the blood pressure and also arresting of heart muscle. HMGB1 is a member of High Mobility Group superfamily proteins which all have a common DNA binding. HMGB1 is released as an extracellular signaling molecule and it binds to Toll like receptors at the cell membrane in the brain cells inflammations. Totally it leads to increase the cytokines and it also intensifies the inflammation. More inflammation can cause the brain cells apoptosis such as neurons and neuroglia cells. Rosamirinic acid, Tanshinone A and Tricin-7 Glucoside which were used for inhibition of HMGB1, they were studied using the Molegro virtual docker ans LiganScout softwares in this study. According to the scores, results showed that Tricin- 7 Glucoside had better physical and spatial interactions with HMGB1 and TLR2 than others and also Tanshinone A had the best interaction with TLR4.

Introduction: A variety of oxygen-transport and -binding proteins exist in organisms including bacteria, protozoans, and fungi all have hemoglobin-like proteins. In addition to dealing with transport and sensing of oxygen, they may also deal with NO2, CO2, sulfide compounds, and even O2 scavenging in environments. Also they detoxified chlorinated materials like P450 enzymes and peroxidases and use as a detector of nitrate and hydrogen peroxide. Pore-forming bacterial globins are interested for filtration.Materials and methods: Although there are data for bacterial toxin as a filter, here we used Agrobacterial hem to induce nano pore in the heme structure using point mutation.Results: Investigations showed that three amino acids leucine 76, alanine 83 and histidine 80 are important for pore formation in Agrobacterium hemoglobin. A point mutation on leucine 76 to glycine, histidine 80 to asparagine and alanine 83 to lysine step by step led to create the nano pore 0.7-0.8 nm in the globin.Discussion and conclusion: These mutations in bacterial hemoglobin increase the stability when mutation is with it’s at pH7. This mutation decreases the aliphatic index however increase the stability index.

Molecular docking which provides useful information on drug-receptor interactions has been frequently used to predict the binding orientation of small molecules to their protein targets. In the current study molecular docking was performed to understand the binding site and the mode of interactions between human serum albumin (HSA) and four newly synthesis Pt complexes, including two platinum (II) complexes with non-leaving lipophilic ligands; deprotonated 2-phenylpyridine (ppy): C1 and deprotonated benzo [h] quinolone (bhq): C2 and two Pt (IV) complexes with the general formula [Pt (X) 2Me2 (tbu2bpy)], where tbu2bpy=4, 4′-ditert-butyl-2, 2′-bipyridine, with two leaving groups of X=Cl: C3 or Br: C4. The crystal structure of HSA was taken from protein data bank (PDB). The molecular docking of the Pt complexes with HSA was calculated by Molegro virtual docker (MVD) software. The potent binding sites with expanded Van der Waals surfaces which known as cavities were nominated to extend the grids over the probable binding sites. At a grid resolution of 0.30   Å, the MolDock scoring functions were adjusted as to give 30 final poses. Each pose suggests the best binding conformation, energy and binding site of the drug into HSA in a cycle of runs. The results of in silico molecular docking study suggest the involvement of  p-p stacking and hydrophobic interactions between HSA and Pt (II) complexes. Also, these results confirm the existence of steric effects and hydrogen bonding interaction between albumin and Pt (IV) complexes. Moreover, the interaction of synthetic Pt complexes occurs in the area between sub-domains IIA and IB.

Objectives Mucopolysaccharidosis IIIB (MPS IIIB) (Sanfilippo Syndrome Type B; OMIM 252920) is an autosomal recessive metabolic disorder caused by mutations in the NAGLU gene which encode lysosomal enzyme N-acetyl-glucosaminidase, involved in degradation of complex polysaccharide, heparan sulfate. The disease is characterized by progressive cognitive decline and behavioral difficulties and motor function retardation. Materials & Methods In this study, targeted exome sequencing was used in consanguineous parent (mother) of a deceased child with clinical diagnosis of mucopolysaccharidosis. Sanger sequencing was performed to confirm the candidate pathogenic variants in extended family members and segregation analysis. In silico pathogenicity assessment of detected variant using multiple computational predictive tools were performed. Computational docking using the Molegro virtual docker (MVD) 6. 0. 1 software applied to evaluate affinity binding of altered protein for its ligand, N-Acetyl-D-Glucosamine. Moreover, with I-TASSER software functional alterations between wild and mutant proteins evaluated. Results We identifi ed a novel heterozygote deletion variant (c. 1294-1304 del CTCTTCCCCAA, p. 432LeufsX25) in the NAGLU gene. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. Computational docking with the Molegro virtual docker (MVD) 6. 0. 1 software confirmed different affinity binding of truncated protein for its ligand. Moreover, I-TASSER software revealed structural and functional alterations of mutant proteins. Conclusion This study expands the spectrum of NAGLU pathogenic variants and confirms the utility of targeted NGS sequencing in genetic diagnosis and also the utility and power of additional family information.

Background & Objective: Alpha-amylase and alpha-glucosidase enzymes raise blood glucose levels by breaking down complex polysaccharide units into absorbable monosaccharide units. The aim of this study was to investigate the inhibitory effect of compounds extracted from Descurainia sophia flowers on the activity of alpha-amylase and alpha-glucosidase enzymes in silico. Material & Methods: This study was performed using descriptive-analytical method. For this purpose, first the compounds extracted from Descurainia sophia flower in the previous study were taken from PubChem databases and then the files related to alpha-amylase and alpha-glucosidase enzymes were obtained from PDB database. The Lipinsky rules and physicochemical properties of the compounds were then predicted by the Zink database and the Swiss ADME server, respectively. Finally, Molegro virtual docker 6. 0 and Molegro Molecular Viewer 2. 5 were used to perform molecular docking tasks. Results: The results showed that most of the compounds present in D. sophia flower had favorable physicochemical properties, and these compounds inhibited α-amylase and α-glucosidase enzymes. But among these compounds, the Valtrate composition with-83. 45 kJ/mol had the most inhibitory effect on the α-amylase enzyme. Similarly, Palatinol and Valtrate compounds had the highest inhibitory effect on the α-glucosidase enzyme with-122. 19 and-152. 88 kJ/ mol, respectively. Conclusion: From the results of this descriptive-analytic study, it can be concluded that the combination of Valtrate due to the appropriate filled in activat site of α-glucosidase and α-amylase enzymes was more effective than the other compounds in D. sophia flower.

This study employed quantitative structure-activity relationship (QSAR) to predict the inhibitory activities of N-(alkyl/aryl)-2-chloro-4-nitro-5-[(4-nitrophenyl) sulfamoyl] benzamide derivatives as potent inhibitors of C-terminal human intestinal maltase-glucoamylase (MGAM-C). Density Functional Theory with B3LYP/6-31G* as the basis set was used to optimize the chemical structures of the derivatives. Genetic function approximation generated three models, with model one having validation keys of R2int= 0.989, R2adj = 0.984, Q2cv = 0.974, and LOF = 0.0056 being selected as the best due to it highest external validation parameter of R2ext = 0.722. The ligand-based approach designed four compounds with higher activities than the lead compound. The binding interactions of the designed compounds within the active site of (MGAM-C) revealed interesting MolDock scores. This research concluded that the designed compounds from the derivatives could serve as potent inhibitors of MGAM-C, offering valuable insight into developing novel medications to treat diabetes mellitus.