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Clinical inhibitors of cell-cycle regulatory enzyme cyclin-dependent kinase 6 (CDK6) are not free of harmful consequences to human bodies. Flavonoids fisetin and chrysin bestow anti-cancer benefits by inhibiting the activities of CDK6 with strong binding affinities. To understand the structure requirement of such inhibitory behaviour, docking and molecular dynamics (MD) simulations were performed on chosen three derivatives each of fisetin and chrysin along with the parent flavonoids. Docking studies revealed more negative binding energies of the derivatives than the parent molecules. MD simulations suggested appreciable stability of the derivatives in the systems. CDK6 association with ring A OH was minute in fisetin, replacing the same with one α-naphtha group in fisetin_3 resulting in enhanced long-range interactions. Interaction of ring A OH groups was significant in chrysin. The additional fluorine atom along with ring C OH and OCH3substituents in chrysin_2 induced a greater number of favourable interactions with CDK6. The selected ligands were docked into the ATP competitive binding site of rigid receptor CDK6/cyclin D using AutoDock 4.2. Stable conformations of the ligands were searched using Lamarckian Genetic Algorithm. Lowest energy poses of the best docked derivatives that resembled experimental conformation of co-crystallised ligand fisetin (fisetin_3, chrysin_3 and chrysin_2), along with fisetin and chrysin which were subjected to MD simulations. Ligand protein interactions in an aqueous environment were modelled using CHARMM27 force field accommodated in GROMACS 2022. MM-PBSA binding free energies of the ligands to CDK6 were computed using g_mmpbsa module of GROMACS. [ABSTRACT FROM AUTHOR]

The partial oxidation of methane to methanol using cationic Pd2 dimers is investigated by employing density functional theory (DFT) method. We used B3PW91 functional for geometry optimization, and frequency calculations of all species involved in [Pd2]++O2+2CH4 reaction. Furthermore, a density‐fitting triple zeta valence with single‐polarization (def2TZVP) is used in the calculation to determine the atomic orbitals of the atoms. We oxidized Pd2+ to [Pd2O2]+ using O2 and performed possible partial oxidation of methane to methanol on [Pd2O2]+ and [Pd2O]+ and explored various intermediates and transition states on the potential energy surface (PES) diagram. From Potential Energy Surface (PES) analysis, it is found that the [Pd2O2]+ in doublet spin state multiplicity (SM=2) following radical mechanism is the more preferred pathway for methane to methanol conversion. [ABSTRACT FROM AUTHOR]

• Catalytic oxidation of NO over pure and doped Au n Pt 3-n (n = 0–3) clusters using Langmuir-Hinshelwood mechanism. • A local M06L Minnesota functional along with valence quadruple- zeta def2QZVPP basis set is utilized for calculations. • Single as well as co-adsorption energies of NO and O 2 over Au n Pt 3-n (n = 0–3) clusters are calculated. • Energetic span model calculation is done to find the efficiency of the clusters. • Mechanisms as well as kinetics for each step of the reaction are reported. A systematic density functional theory (DFT) calculations are performed on pure as well as doped Au 3 trimer clusters to study the catalytic oxidation of NO to NO 2 using the M06L functional combined with a def2QZVPP basis set. Adsorption energies and Bader charges of adsorbed NO and O 2 on the Au n Pt 3-n clusters have been calculated to observe the stability of the adsorbed species. Results show that the adsorption of both NO and O 2 on the bimetallic clusters is stronger on the Pt site than that of Au site. Owing to the high adsorption energy of both the reactants, we further propose a reaction mechanism of NO oxidation over Au n Pt 3-n (n = 0–3) clusters following the Langmuir-Hinshelwood (L-H) mechanism. The rate constants of NO 2 production at each step of the reaction mechanism are determined using the Transition State Theory (TST). Energetic span model is also used to determine the efficient catalytic system among the four clusters. This study offers a new insight into the fundamental effect of doping Pt on Au 3 and conveys an understanding for the NO oxidation mechanism at the molecular level which in turn will help in building efficient catalysts for large-scale processes. [Display omitted] [ABSTRACT FROM AUTHOR]

In the present study, five novel LNA based antisense modifications have been proposed. A conformational search was carried out using TANGO, followed by geometry optimization using MOPAC. Based on their electronic energies the most stable conformation for each modification was identified. Further, DFT based full geometry optimization on the most stable conformations at the gas phase B3LYP/6-31G(d,p) using a Gaussian03 and single point energy calculations on the optimized structures at the solvent phase B3LYP/6-311G(d,p) level of theory were done to derive their quantum chemical descriptors using the Gaussian09. A comparison of global reactivity descriptors confirmed that the LNA based modifications were the most reactive. Base-pair stability was recorded by observing the binding energies and base-pairing conformations of modified GC base pairs at the B3LYP/6-311G(d,p) level of theory. Molecular dynamics simulations have been performed at the oligomer duplex level by incorporating individual modifications on 20-mer RNA-RNA duplexes using AMBER16. Free energy calculations of duplex structures suggested that incorporation of A2 modification into the RNA-RNA duplex increased the duplex binding affinity similar to LNA. Whereas, the A3 modification showed less binding compared to LNA but improved binding compared to MOE. This computational approach using quantum chemical methods may be very useful to propose better modifications than the existing ones before performing the experiments in the area of antisense technology. [Display omitted] • LNA, MOE and LNA-based modifications were studied by quantum chemical calculations. • Most stable conformation for all these modifications was identified by conformational search. • LNA and LNA-based modifications are more suitable compared to others. • MD simulations were carried out on oligomer duplexes with modifications incorporated. • The proposed modification A3 has shown similar properties with LNA modification. [ABSTRACT FROM AUTHOR]

A comprehensive density functional theory (DFT) investigation of the catalytic oxidation of NO to NO2 on neutral and charged [Pt2]0,± dimers has been considered employing M06L/def2TZVP level of theory. Single as well as co‐adsorption energies of NO and O2 molecules suggest that the traditional Langmuir Hinshelwood (LH) mechanism and less explored termolecular Eley–Rideal (TER) and termolecular Langmuir Hinshelwood (TLH) mechanisms, are suitable for a full catalytic reaction pathway in which two NO molecules are converted to two NO2 molecules, initiated by an activated O2 molecule. Activation barrier reveals that the TER mechanism is found to be more reliable in converting two NO molecules into two NO2 molecules on [Pt2]¯ dimer. In addition to shedding light on the intrinsic characteristics of Pt2 dimers, the study will serve as a benchmark for investigating the oxidation process of NO to NO2 utilizing models of termolecular chemical processes. [ABSTRACT FROM AUTHOR]

The present study describes the facile synthesis and comprehensive characterization of new oxido and peroxidoniobium(V) complexes with biogenic ligands, maltol (malt) and deferiprone (def) in their co-ordination sphere, viz., [NbO(malt)3]2·9H2O (1), Na2[Nb(O2)3(malt)]·H2O (2) and Na2[Nb(O2)3(def)]·2H2O (3). The complexes were characterized using various analytical and spectroscopic techniques (FTIR, Raman, NMR, UV-visible, TGA, ICP-OES and elemental analysis). The charge neutral complex 1 was further characterized by single crystal XRD analysis, and the proposed structures of the peroxidoniobium (pNb) complexes 2 and 3 were validated by density functional theory (DFT) studies. A comparative investigation on the in vitro effect of the title compounds and a set of previously reported polymer-anchored peroxidoniobium complexes, [Nb(O2)3(sulfonate)2]3−-PSS [PSS = poly(sodium 4-styrene sulfonate)] (5), [Nb2(O2)6(carboxylate)2]4−-PA [PA = poly(sodium acrylate)] (6) and [Nb(O2)3(carboxylate)]2−-PMA [PMA = poly(sodium methacrylate)] (7), on the activity of the model enzyme wheat thylakoid acid phosphatase has revealed that each of the compounds is an effective inhibitor of the enzyme (IC50 values varying within the range 1–64 μM). The results of the detailed enzyme kinetic study demonstrated that the compounds induce their inhibitory effect via distinct pathways. The oxidoniobium complex 1 as well as polymer-anchored pNb complexes acted as classical non-competitive inhibitors of ACP, whereas the monomeric pNb complexes emerged as mixed inhibitors of the enzyme (Kii > Ki). Notably, the complexes serve as excellent recyclable catalysts for selective styrene epoxidation with H2O2, affording 99% styrene conversion, ≥98% epoxide selectivity and a high turnover number of 1740 under eco-friendly solventless conditions. [ABSTRACT FROM AUTHOR]

All approved coronavirus disease 2019 (COVID-19) vaccines in current use are safe, effective, and reduce the risk of severe illness. Although data on the immunological presentation of patients with COVID-19 is limited, increasing experimental evidence supports the significant contribution of B and T cells towards the resolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite the availability of several COVID-19 vaccines with high efficacy, more effective vaccines are still needed to protect against the new variants of SARS-CoV-2. Employing a comprehensive immunoinformatic prediction algorithm and leveraging the genetic closeness with SARS-CoV, we have predicted potential immune epitopes in the structural proteins of SARS-CoV-2. The S and N proteins of SARS-CoV-2 and SARS-CoVs are main targets of antibody detection and have motivated us to design four multi-epitope vaccines which were based on our predicted B- and T-cell epitopes of SARS-CoV-2 structural proteins. The cardinal epitopes selected for the vaccine constructs are predicted to possess antigenic, non-allergenic, and cytokine-inducing properties. Additionally, some of the predicted epitopes have been experimentally validated in published papers. Furthermore, we used the C-ImmSim server to predict effective immune responses induced by the epitope-based vaccines. Taken together, the immune epitopes predicted in this study provide a platform for future experimental validations which may facilitate the development of effective vaccine candidates and epitope-based serological diagnostic assays. [ABSTRACT FROM AUTHOR]