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Halogenated Schiff base derivatives are gaining more popularity in supramolecular chemistry due to the synergistic effect of hydrogen and halogen-based noncovalent interactions, which helps to design novel therapeutic materials. In this work, we have examined the nature of molecular interactions to investigate the structure-functional relationship of a halogen-based derivative. The FTIR, HRMS and NMR spectroscopic techniques confirmed the formation of the desired novel Schiff base compound. Further, crystal structure studies showed an infinite 1D supramolecular chain formed by type-I halogen…halogen interaction. The Hirshfeld surface and enrichment ratio analyses were performed to visualize and assess the role of diverse interactions involved in crystal packing. The QTAIM, NCI, LOL and ELF studies were conducted extensively to comprehend the strength of interaction constructed based on electron density distribution. The global and local reactive indices were determined using DFT studies to analyze the molecular properties of the compound. Antibacterial activity against MRSA bacteria was performed and showed a good zone of inhibition. The docking analysis was performed for 1mwt protein and validated. The in silico molecular docking studies of the halogenated Schiff base structure with the penicillin-binding protein showed a good docking affinity of -7.5 kcal/mol and supported by in vitro studies. The ligand binding stability within the protein's active site was further demonstrated by molecular dynamics (MD) simulation studies for the Schiff base molecule.Communicated by Ramaswamy H. Sarma.

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A novel mixed ligand Ni(II) metal complex has been investigated for the modification in structural conformation, coordination bond, and noncovalent interactions. The novel Ni(II) metal complex [Ni(TFPB)2(1,10-Ph)(DMF)] has been synthesized and structurally characterized, which featured six coordination with three bidentate ligands connected through oxygen and nitrogen atoms. The single-crystal X-ray analysis showed that the compound possessed octahedral geometry and C-H…F, C-H…O, and π…π intermolecular interactions resulting in the formation of supramolecular architecture contributed significantly towards the crystal packing and molecular stability. Hirshfeld surface analysis was carried out to validate various intermolecular interactions. Further, the 3D structural topologies were visualized using energy framework analysis. To explore the coordination stability and chemically reactive parameters of the novel Ni(II) complex, the electronic structure was optimized using density functional theory calculations. The natural bond orbital analysis revealed the various hyperconjugative interactions exhibited by the complex. In addition, the complex was screened for in silico studies to understand the antitumoricidal potential of the novel Ni(II) complex. Molecular docking studies were also performed against three targeted proteins (PDB ID: 6H0W, 6NE5, and 6E91) to investigate the binding mode and protein-ligand interactions. These results are further analyzed by molecular dynamic simulation to confirm the best possible interactions and stability in the active site of the targeted proteins with a simulation period of 100 ns.Communicated by Ramaswamy H. Sarma.

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In December 2019, a new type of SARS corona virus emerged from China and caused a globally pandemic corona virus disease (COVID-19). This highly infectious virus has been named as SARS-CoV-2 by the International Committee of the Taxonomy of Viruses. It has severely affected a large population and economy worldwide. Globally various scientific communities have been involved in studying this newly emerged virus and is lifecycle. Multiple diverse studies are in progress to design novel therapeutic agents, in which understanding of interactions between the target and drug ligand is a significant key for this challenge. Structures of proteins involved in the life cycle of the virus have been revealed in RCSB PDB by researchers. In this study, we employed molecular docking study of 4-Acetamido-3-nitrobenzoic acid (ANBA) with corona virus proteins (spike protein, spike binding domain with ACE2 receptor and Main protease, RNA-dependent RNA polymerase). Single crystal X-ray analysis and density functional theory calculations were carried out for ANBA to explore the structural and chemical-reactive parameters. Intermolecular interactions which are involved in the ligand-protein binding process are validated by Hirshfeld surface analysis. To study the behaviour of ANBA in a living organism and to calculate the physicochemical parameters, ADMET analysis was done using SwissADME and Osiris data warrior tools. Further, Toxicity of ANBA was predicted using pkCSM online software. Based on the molecular docking analysis, we introduce here a potent drug molecule that binds to the COVID-19 proteins.Communicated by Ramaswamy H. Sarma.

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Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Šusing X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II). The cofactor (SAM) molecule binds at the interface between adjacent subunits, presumably near to the active site(s) of the enzyme. The observed dimeric state might be important for the catalytic function of the enzyme.

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