Aptamer biosensor design for the detection of endocrine-disrupting chemicals small organic molecules using novel bioinformatics methods.

Endocrine-disrupting chemicals (EDCs) are substances that can disrupt the normal functioning of hormones.Using aptamers, which are biological recognition elements, biosensors can quickly and accurately detect EDCs in environmental samples. However, the elucidation of aptamer structures by conventional methods is highly challenging due to their complexity. This has led to the development of three-dimensional aptamer structures based on different models and techniques. To do this, we developed a way to predict the 3D structures of the SS DNA needed for this sequence by starting with an aptamer sequence that has biosensor properties specific to bisphenol-A (BPA), one of the chemicals found in water samples that can interfere with hormones. In addition, we will elucidate the intermolecular mechanisms and binding affinity between aptamers and endocrine disruptors using bioinformatics techniques such as molecular docking, molecular dynamics simulation, and binding energies. The outcomes of our study are to compare modeling programs and force fields to see how reliable they are and how well they agree with results found in the existing literature, to understand the intermolecular mechanisms and affinity of aptamer-based biosensors, and to find a new way to make aptamers that takes less time and costs less.

Molecular structure determination, spectroscopic, quantum computational studies and molecular docking of 4-(E)-[2-(benzylamino)phenylimino) methyl-2]ethoxy phenol.

A Schiff base compound 4-(E)-[2-(benzylamino)phenylimino)methyl-2]ethoxy phenol (4BPM2EP) was synthesized and spectroscopic characterization was performed using experimental methods such as FT-IR, FT-Raman and UV-Vis spectroscopy. Density functional theory (DFT/B3LYP/6-311++G(d,p)) computation was used to investigate the optimized molecular geometry, harmonic vibrational wavenumber, NMR chemical shifts, natural bond orbital (NBO) analysis, non-linear optical (NLO) properties, molecular electrostatic potential (MEP) map and Mulliken atomic charges of 4BPM2EP molecule. TD-DFT calculations have been carried out on the optimized geometry at gaseous phase, DMSO and ethanol to further understand the electronic transitions and solvents effect on the UV-Vis spectra of the compound. The assignments of vibrational modes were performed on the basis of total energy distribution (TED) using VEDA 4 program and were compared with experimental data. Molecular docking study was performed using Glide program to establish the information about the interactions between the topoisomerase DNA gyrase enzymes and the novel compound in order to explore the biological behaviour of the examined compound. The compound screened against four pathogens two gram positive, two gram negative and two fungal strains had shown good anti-bacterial and antifungal behaviour. Furthermore the compound was subjected to in-silico ADMET studies.Communicated by Ramaswamy H. Sarma.

Structural, vibrational spectroscopy, molecular docking, DFT studies and antibacterial activity of (E)-N1-(3-chlorobenzylidene)benzene-1,4-diamine.

In this work, (E)-N1-(3-chlorobenzylidene)benzene-1,4-diamine (CBD) compound was synthesized with good yield. The spectral studies were recorded by FT-IR, FT-Raman, NMR and UV-Vis to determine structural parameters. The geometrical parameters were optimized using DFT calculations at 6-311++G(d,p) basis set. The calculated structural parameters of the molecule were in line with the experimental data. The molecular orbitals of the compound were investigated through highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO) analysis. The hyper conjugative interaction energy E(2) along with donor, acceptor electron densities (EDs) were determined by natural bond orbital (NBO) analysis. The molecular electrostatic potential (MEP), mulliken atomic charges, non-linear optical (NLO) properties and potential energy surface (PES) scan were also calculated. The 1H and 13C NMR chemical shifts calculated using Gauge invariant atomic orbital (GIAO) method were compared with the experimental NMR chemical shifts. Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC) were carried out to characterise the thermal behaviour and stability of CBD molecule. In addition, PreADMET tool was also used to estimate ADME and Toxicity of CBD compound. The compound screened against four pathogens two gram positive and two gram negative had shown good anti-bacterial behaviour. The molecular docking studies executed against anti-bacterial target topoisomerase DNA gyrase enzyme (2XCT) emphasized good binding behaviour over the standard drug.Communicated by Ramaswamy H. Sarma.

Synthesis and characterization of a novel Mannich base benzimidazole derivative to explore interaction with human serum albumin and antimicrobial property: experimental and theoretical approach.

The novel Mannich base benzimidazole derivative (CB-1), 1-((1H-benzo[d]imidazol-1-yl)(3-chlorophenyl)methyl)-3-phenylurea) has been designed and synthesized by reacting benzimidazole, 3-chloro benzaldehyde, and N-Phenyl urea. CB-1 has been characterized by UV- Visible, FTIR, and 1H NMR. CB-1 was explored to study the interaction with the most abundant blood protein which involved in the role of transport of molecules (drugs), human serum albumin (HSA). Fluorescence results are evident for the presence of both dynamic and static quenching mechanisms in the binding of CB-1 to HSA. Antimicrobial screening were carried out against three bacteria and three fungi pathogens employing disc diffusion method. Molecular docking using AutoDock Vina tool further confirms the experimental binding interactions obtained from fluorescence. Density functional theory (DFT) with B3LYP/6-311G++ basis set was used for correlating theoretical data and obtaining optimized structures of CB-1 along with reactants with molecular electrostatic potential (MEP) map and HOMO→LUMO energy gap calculation. HIGHLIGHTSThe novel Mannich base benzimidazole derivative (CB-1) has been designed and synthesized by Mannich reaction.CB-1 has been characterized by UV- Visible, FTIR, and 1H NMR.Fluorescence quenching reveals that HSA binds to CB-1 via aromatic residues, which is corroborated by molecular docking.Antifungal and antibacterial activity was evaluated in comparison to Nystatin and Gentamicin standard drugs, respectively.DFT calculations support experimental data and provide HOMO-LUMO energy gap.Communicated by Ramaswamy H. Sarma.