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.

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.

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.