Hossein Tavakol

In this study, with the aim of designing novel therapeutics to inhibit monoamine oxidase A and finding the effect of structural parameters on this effect, 70 new ligands, consisted of 16 different substituents were designed to evaluate their inhibitory effects on monoamine oxidase A and compare their results with 18 existed reference drugs and hormones, thereby laying the groundwork for the introduction of potential new pharmaceutical agents. Ultimately, by comparing interaction energies, from the molecular docking calculations, and pharmacokinetic parameters, six ligands were proposed as candidates for monoamine oxidase A inhibition. These ligands were subjected to further investigation via 300 ns molecular dynamics simulations using GROMACS. The obtained trajectories were analyzed by protein RMSD, ligand RMSD, protein RMSF, ligand RMSF, Rg, SASA, min distance, PCA analysis, hydrogen bond analyses, and MM-PBSA. All the analyses showed the stability, good binding, small structural changes, which all of them propose the studied ligands are suitable candidates for the inhibition of MAO-A enzyme. To choose the best candidates, an AI-guided multi-parameter scoring framework was designed, including the weighted results of 12 analyses. Observing the final scores revealed that 4-position and NHAc ligands get the higher scores while 2-position get the least scores.

Quantum mechanical (QM) calculations, molecular docking, and molecular dynamics (MD) simulations were performed to elucidate the influence of structural modifications on the binding affinity of newly designed monoamine oxidase B (MAO-B) inhibitors. In this line, after the optimizations of the structures of 70 new ligands and 15 reference compounds (existed drugs and hormones) using QM calculations, their interactions were analyzed by docking calculations to select the final 5 most appropriate ligands. These ligands were investigated by 300 ns MD simulations and the resulted trajectories were investigated using primary, structural (RMSD, RMSF, Rg, SASA, mindist, PCA), and interaction (hydrogen bonding and M-PBSA) analyzes. The results were promising, since all systems showed proper stability of the whole systems and significant interactions between the ligand and protein. To identify the most promising inhibitor candidates, in addition to comparing systems by considering equal contributions for each analysis, a weighted multi-parameter scoring framework was developed by integrating the results of twelve computational analyses, with each parameter assigned an appropriate weighting according to its relative importance. Noticeably, both scoring systems presented the similar ligand as the best inhibitor: 3OAc. In fact, meta position of the substituent and more electronegative substituent are the important factors which affect the interaction between the ligand and protein to be a more useful inhibitor.

During the present study, single-atom catalysts (SACs) were designed by decorating graphitic carbon nitride with copper (I) and nickel (I) ions. The designed catalysts were employed for studying the possible reaction pathways for benzene to phenol oxidation. The calculations were carried out using the density functional theory (DFT) method at the M06-2X/def2-SVP level of theory. To select the catalyst among various spin multiplicities and decoration places, the relative energies, interaction energies, and energy gaps were compared, which showed the smaller spin multiplicity and center position of the decorated metal was the most suitable case for both SACs. To investigate the reaction process, two possible routes were considered and the relative energies and Gibbs free energies of all involved species in these pathways were calculated in the gas phase. The gas phase energies confirmed the reliability of the proposed routes and the higher ability of Ni-based SAC than Cu-based SAC by both thermodynamic and kinetic data. To consider the solvent effects, the polarizable continuum model(PCM) was employed using acetonitrile and methanol as two common solvents. The obtained energy values in solvents confirmed the higher potency of Ni SAC versus Cu SAC for this reaction and both solvents showed nearly similar overall barriers and thermodynamic values.

In this report, the reaction mechanism of triphenylphosphite addition to β‐nitrostyrene is theoretically investigated. The M062X method, a subset of density functional theory (DFT), and the def2svp basis set are used to determine the appropriate mechanism. Three plausible mechanistic routes, labeled pathways A, B, and C, are proposed. In pathway A, triphenyl phosphite is added to the β‐position of β‐nitrostyrene. Pathway B involves the addition of the triphenyl phosphite molecule to the oxygen of the nitro group in β‐nitrostyrene. In pathway C, triphenyl phosphite is added to the nitrogen of the β‐nitrostyrene compound. Since the reaction requires the presence of two mmol of triphenyl phosphite to form the desired product, all three routes of the proposed mechanism are designed accordingly. In the gas phase, the overall energy barriers of paths A and B are 19.31 and 43.47 kcal mol⁻¹, respectively, while no reliable transition state is obtained for path C. For path A in different solvents, the overall energy barriers are 20.75, 20.76, and 20.76 kcal mol⁻¹, respectively in water, methanol, and dimethylformamide. Therefore, path A is a more favorable path, and there is not a meaningful difference between the results of the gas phase and different solvents.