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Investigating the molecular structure, vibration methods, nonlinear optical, electronic and thermo dynamical properties of 2, 4-dichloroaniline (2, 4DCA), 2, 4-difluoroaniline (2, 4DFA) and 2, 4-diiodoaniline (2, 4DIA) gives comparable hypothetical properties to decide a desired material. Density Functional Theories (DFTs) have the basic guidelines to affect the Schrödinger equation for several body systems. Comparison is drawn among theoretical properties like stability and charge delocalization of the molecules which are studied by Natural Bond Orbital (NBO) analysis, Nonlinear Optical (NLO) behavior in terms of first-order hyperpolarizability, Molecular Electrostatic Potential (MEP) and dipole moment of title compounds. The chance of the title atoms being bio-active hypothetically incontestable by the electrophilicity index prompts additional property studies for the chosen compounds. The title molecules are found to suit well with L – glutamate oxidase inhibitor utilizing molecular docking techniques. The outcomes of the chosen organic alkane series are obtained utilizing higher basis set (6-311++G (d, 2p)) to realize results.

Prevotella copri is a prominent constituent of the human gastrointestinal microbiome, and its fluctuating abundance has been linked with positive and negative influences on diseases such as Parkinson’s disease and rheumatoid arthritis. Prevotella copri demonstrates flexibility against drugs. There is presently no vaccine approved by the FDA against prevotella copri,and treatment options are restricted. Hence, this research work was designed to create an in silico-based vaccine for prevotella copri.The protein sequences of two distinct strains ofprevotella copriwere retrieved from NCBI. The T-cell and B-cell epitopes were obtained and then analyzed for antigenicity, allergenicity, docking and simulation. The peptide comprises linear B-cell and T-cell epitopes from proteins identified as potential novel vaccine candidates. The molecular dynamics (MD) simulations and protein-protein docking results revealed that the vaccine exhibits strong and Sustained interaction with Toll-like receptor 4 (TLR4). The constructed sequence was integrated into the pET-30a (+) biological vehicle (vector) for subsequent analysis expression in E. coli through the SnapGene server. The constructed multi-epitopic vaccine candidate was assessed for its structural, physicochemical and immunological properties. The results demonstrated solubility, stability, antigenicity and nonallergenicity and showed a strong affinity for its target receptors. The in silico study represents a significant step forward in designing a vaccine that could effectively eliminate Prevotella copri globally.

Here, we provide the synthesis process as well as theoretical and experimental research on the molecule known as 7-hydroxy-2-(3,4-dihydroxyphenyl)-3-(piperidin-4-yloxy)-4H-chromen-4-one (7THFP). Quantum mechanical calculations (QM) using several functional levels at a standard basis set have been used to calculate all QM calculations and molecular descriptors. Computational techniques were used to obtain the whole range of vibrational frequencies, IR intensity and Raman activity, all showing excellent agreement with the observed results. The molecule’s electron transport characteristics were explained by Mulliken, NBO, mapped isosurface electron density and Highest Occupied Molecular Orbitals (HOMO)-Lowest Unoccupied Molecular Orbitals (LUMO) investigations. The energy difference between the molecular orbitals (MOs) has also been anticipated. The drug candidate’s ADMET and Lipinski’s rule of five models were used to predict its physicochemical and pharmacokinetic properties, including bioactivity score, lipophilicity and toxicity profiles. The physicochemical profiles of 7THFP indicate favorable drug-likeness, bioactivity and reduced toxicity. Subsequently, molecular docking (MD) analyses were conducted to forecast the ligand’s inhibitory impact on the enzymes. The docking score estimation and in vitro analysis of the drug compound validate its anticancer activity. Lastly, the title molecule was evaluated for its proliferation and cytotoxicity effects on human MCF-7 cell lines. These investigations demonstrate that the product exhibits promising characteristics as a drug candidate and may serve as a model for further enhancement.

The single crystalline diethyl 3,3${}^{\prime }$-[(2,4-dichlorophenyl)methylidene]bis(1H-indole-2-carboxylate) (D32DMBC) samples are fully grown-up in a proper and in a successful manner by the prevailing slowly evaporating methodology. The lattice cell frameworks by XRD modus operandi also corroborated that the D32DMBC crystal system is monoclinic in nature. The structural properties by a conceptual way authenticate the elucidation and also the proper vindication for bond parameters. The nano influx is 3.2768 micron and the film-coated influx of 2.9977 microns as a mid-value between the macro as well as the nano assessment is suitable for electronic filters by D32DMBC crystals, and also used for tribological-coated utility as well as in frequency multipliers. Diabetes mellitus is the repetitive disease in the way of life and sustaining approach of D32DMBC — organic crystals are properly, accurately experimented by the use of the software pertaining to the D32DMBC by docking effect. The affinity inhibitory activity of A74DME and exploratory molecule of D32DMBC are −8.1kJ/mole and −8.4kJ/mole correspondingly. The computational effect of Hirshfeld portrays the internal/external fields as well as the electron higher/lower profile in the shape index proviso for optical utility identification and proper electronic utility.

Large allograft bones are commonly used in limb salvage procedures for the reconstruction of bone defects after resection of a bone tumor. A V-shaped osteotomy may perform better than the traditional transverse osteotomy as it increases the stability of the docking site and increases the contact area between an allograft and the host cortex. The aim of this study is to investigate the biomechanical properties of a V-shaped docking site of different angles.

orcine femurs with 45°, 60° or 90° V-shaped osteotomy were first tested with 1000 N compression, followed by 2 and 5 Nm torque. The torsional stiffness of the 45° specimen group at 5 Nm torque was significantly higher (P<0.05) than the 90° group. Therefore, our results show that 45° V-shaped osteotomy is found to be the most stable docking angle.

By means of the Homology modeling and the known structure of cyannogenic β-glycosidase from white clover (1CBG, EC 3.2.1.21), we construct a 3D model of the β-primeverosidase (EC 3.2.1.149) and search for the binding site of substrate. The 3D model is then refined by using molecular mechanics (optimization and molecular dynamics) simulation. Finally, the refined model is further assessed by Profile-3D and PROCHECK, and the results showed that the final model is reliable. Furthermore, the docking of the substrates into the active site of the protein indicates that β-primeverosidase is able to hydrolyze β-primeverosides, but not act on 2-phenylethyl β-D-glucopyranoside. These results suggest that β-primeverosidase shows broad substrate specificity with respect to the disaccharide glycon moiety (subsite -2). This is consistent with the experimental observation. Thr271 and Thr415 play important roles in subsite -2 of β-primeverosidase. Our results may be helpful for further experimental investigations.

Molecular dynamics, density functional with correlation, as well as docking studies of inhibitors of HIV-1 reverse transcriptase (RT) are reported. We propose in this work a novel potential HIV-1 RT inhibitor (RTI), which theoretically appears to bind in a similar mode as other nucleoside reverse transcriptase inhibitors, and in addition, it introduces a new hydrogen bond interaction with Trp229. Our novel RTI has high docking scores and the molecular dynamics studies, as well as the analysis of the ligand-receptor interactions in the active site and the ADMET properties suggest advantages and specificities for this potential RTI.

With homology-modeling techniques, molecular mechanics and molecular dynamics methods, a 3D structure model of the human inosine triphosphatase (ITPase; EC 3.6.1.19) is created and refined. This model is further assessed by Profile-3D and ProStat, which confirm that the refined model is reliable. With this model, a flexible docking study is performed, and the results indicate that Arg178, Lys19 and Glu44 are three important determinant residues in substrate binding because they have prominent interaction energies with ITP and form strong hydrogen bonds with ITP. In addition, we further find that the P32T substitution alters the α-helices of ITPase but the β-sheets are almost not changed, and the mutation induces the interaction energy between ITPase and ITP to increase, which are consistent with the conclusion predicted by Sumi et al.⁸ The results from the mutagenesis imply that Pro32 is vital for the catalytic activity.

A descriptor, the pose scaling factor, is proposed to quantitatively evaluate the geometrical match between a ligand and a target binding site. The pose scaling factor can be used to readily rank results of target-based in silico database screening or docking on large numbers of compounds. Such an approach will be of utility in the development and refinement of docking algorithms.

Two novel matrix metalloproteinase (MMP) inhibitors, myricetin (m) and kaempferol (k), were found and the inhibitory activity is both in decreased order towards MMP-2 and MMP-9. To understand the mechanism during the processes when inhibitors bind to MMP-2 and MMP-9, molecular modeling, docking, and density functional theory (DFT) calculations were performed. The calculated results indicated that the hydroxyls on benzene ring of the inhibitors control the binding modes between inhibitors and MMPs, thus play an important role on the potency and selectivity. Besides coordinating with the N atoms of three His residues, Zn also interacts with a hydroxyl group of inhibitors by O–Zn distances of 2.66–2.78 Å in all of the docked complexes, so that the hydroxyl acts as a weak zinc binding group (ZBG). The DFT calculated results support the above analysis. The binding affinity calculations between inhibitors and MMPs present the total interaction energies in the m-MMP < k-MMP order and the solvation energy of myricetin is less than that of kaempferol, which reflect the experimental inhibitory activity.

Arylesterases (E.C. 3.1.1.2) play an important role in nature, which show high enantioselectivity toward chemically and pharmaceutically important compound in addition to being environmentally friendly. The docking results indicate that Tyr34, Leu98, Ile64, Met36, and Ile38 have important contributions to the substrate binding and the side chains of these residues can provide a rather vdW interaction with the substrate. The molecular dynamics calculation of the free energy by MM-PBSA method implies that the S31A and S31G mutant enzymes show more stability as compared with the wild type, which is in harmony with the kinetic experiment that the 2-fold and 2.5-fold increase in the K_m for S31A and S31G enzymes. From these results, we can conjecture that mutations of Ser31 make the active site more spacious than that of arylerases', and it can lead to the enzyme active. The new structural insights obtained from this computational study are expected to stimulate further biochemical studies on the structures and mechanisms of other members of the SGNH-hydrolases.

The influenza A (H5N1) virus attracts a worldwide attention and calls for the urgent development of novel antiviral drugs. In this study, explicitly solvated flexible docking and molecular dynamics (MD) simulations were used to study the interactions between the H5N1 sub-type hemagglutinin (HA) and various catechin compounds, including EC ([–]-epicatechin), EGC ([–]-epigallocatechin), ECG ([–]-epicatechin gallate) and EGCG ([–]-epigallocatechin gallate). The four compounds have respective binding specificities and their interaction energies with HA decrease in the order of EGCG (-133.52) > ECG (-111.11) > EGC (-97.94) > EC (-83.39). Units in kcal mol^-1. Residues IleA267, LysA269, ArgB68 and GluB78 play important roles during all the binding processes. EGCG has the best bioactivity and shows potential as a lead compound. Besides, the importance was clarified for the functional groups it was revealed that the C5′ hydroxyl and trihydroxybenzoic acid groups are crucial for the catechin inhibitory activities, especially the latter. Combined with the structural and property analyses, this work also proposed the way to effectively modify the functional groups of EGCG. The experimental efforts are expected in order to actualize the catechin derivatives as novel anti-influenza agents in the near future.

Kynurenine aminotransferase III (KAT III) is a novel member of the kynurenine aminotransferase enzyme family. Its active site topology and structure characteristics have not been established. In this study, with extensive computational simulations, including homology modeling and molecular dynamics simulations, a 3D structure model of human KAT III dimer was created and refined. Furthermore, CDOCKER approach was employed to dock two ligands (L-methionine and L-tryptophan) into the active sites of human KAT III dimer and uncover the ligand-binding modes. The complexes were subjected to 5 ns MD simulation, and the results indicate that TYR119 and TRP13 might be the key residues as they have the large contributions to the binding affinity, which is in good agreement with the experimental results. Moreover, another two residues (ASP120 and TYR57) are also found that their strong interactions stabilize the whole system. The structural and biochemical insights obtained from the present study will be helpful for designing the specific inhibitors of human KAT III.

Inhibitors of histone deacetylases (HDACs) have become an attractive class of anticancer agent. To understand the interaction between HDAC8 and inhibitors, including "pan-" inhibitors that inhibit many HDACs isoforms and selective inhibitors with no linker domain, docking and molecular dynamics simulation were conducted. Docking results showed the presence of π-π interactions between "linkerless" inhibitors and the aromatic amino acid residues of HDAC8 in the active site. Binding between HDAC8 and inhibitors was also stabilized by hydrogen bond and hydrophobic interaction. In molecular dynamics simulations, the zinc ion was shown to coordinate one more atom of HDAC8-"linkerless" inhibitor complexes than HDAC8-"pan-" inhibitor complexes. Persistent hydrogen bonds also existed between Tyr306 of HDAC8 and some inhibitors. When inhibitors with large cap groups bound to the active pocket of HDAC8, Phe152 and Met274 shifted from their initial positions and the entrance of the active pocket became more open, resulting in the formation of sub-pocket. Hydrophobic interactions contributed most favorably to the binding free energy between HDAC8 and inhibitors. Lys33, Asp178, Asp267, Tyr306 and Leu308 of HDAC8 were favorable for binding with all inhibitors.

Through a reductive dimerization of two farnesyl diphosphate (FPP) molecules, Squalene synthase from Panax ginseng (P. ginseng) (PgSS) catalyzes the biosynthesis of squalene, a key cholesterol precutsor, and hence is an attractive site of therapeutic intervention. Thus, the 3D structure of PgSS has been firmly established by homology modeling and was used to relax by MD simulation to get the reliable structure. It is well known that Mg²⁺ plays an important role in substrate binding. Understanding how PgSS recruits the FPP substrate through Mg²⁺ is the first and foremost step toward further mechanistic investigations and the design of effective PgSS inhibitors. Quantum mechanical calculation method is used to determine the Mg²⁺ binding mode. In the first binding motif, the Mg²⁺ ion is coordinated to D77, D81, and one oxygen atom from the α- and β-phosphates of FPP. In order to determine the important residue of the substrate (FPP) binding, we dock the one FPP to the protein. Arg113 may be an important residue because they form a salt bridge with PgSS. After virtual screening technique of PgSS, a novel natural compound (8002215) has been found with the lowest affinity energy. Then we identify that His266 is the most important anchoring residue for binding with 8002215 because it has strong edge-to-face interaction with inhibitor. Leu205 and Gln206 are important residues for they make hydrogen bonds with inhibitor. Our results may be helpful for further experimental investigations.

Quasiclassical Trajectory (QCT) calculation for O(³P) + HD → OH + D and O(³P) + HD → OD + H at E_col = 0.4–1.0 eV and 0.5–1.0 eV, respectively, on the lowest PES 1 ³A″ of Kuppermann et al. has been done. Distribution p(ϑ_r) of azimuthal angles between the relative velocity k of the reactants and rotational angular momentum vector j′ of either OH or OD, p(φ_r) of polar as well as dihedral angles correlating k - k′ -j′, p(ϑ_r, φ_r), and PDDCS dependent upon the scattering angle ϑ_t of either OH, or OD between k and k′ of the reactants and products, respectively, are presented and discussed. The stereodynamics and isotopic mass effects at the smallest possible collision energies 0.4 eV and 0.5 eV for OH and OD, respectively, are significantly different. The significant mass effect with quotient 1/2 of H/D, at the corresponding collision threshold may be applied for the investigation of docking mechanism, drug modification and delivery.

The latest influenza A (H7N9) virus attracted a worldwide attention due to the first report of human infections and the continuing reported cases in China. In this work, homology modeling, docking and molecular dynamics simulations were combined to study the interactions between neuraminidase (N9_2013, from novel A/H7N9 virus) and agents zanamivir, oseltamivir, peramivir. It was found that N9_2013 protein is structurally close to the template (PDB code: 1F8B), especially the active site. The binding properties of N9_2013 protein were nearly identical to those of template. As a result, the three available drugs should be still efficacious for the new emerging A (H7N9) virus. However, the stabilities of docked complexes and binding affinities (E_int) were slightly reduced, in contrast to the corresponding inhibitor-template complexes, with the values of -82.27 (-84.30), -78.84 (-80.28) and -77.52 (-81.94) kcal mol^-1, respectively. Besides, R292K mutation might induce the resistance of the novel virus to the commercial inhibitors. Thus, it arouses the need for continuous monitoring of antiviral drug susceptibilities.

Antibodies play a significant role in the immunotherapy, basic research and the pharmaceutical industry. Nowadays, both DNA recombinant technology and antibody engineering technology are widely used in many fields such as diagnostics, therapeutics, drug targeted delivery, and research reagents. Computational docking of antigen-antibody complexes and analysis of atomic interactions are important to find effective B-cell epitopes and new antibodies with appropriate properties. In the present study, by using ClusPro 2.0 webserver, docking the antigen (factor H binding protein (fHbp)) to the novel-selected scFv antibody was performed. By analyzing the fHbp-scFv complexes, important amino acids were identified. After docking, peptides Ala192-His198, Asp 211-216, and Gly229-Ser228 of the fHbp antigen were recognized as essential interactive regions to the scFv antibody. Results obtained from our bioinformatics study are important and give us the basis for the favored designs of new molecules such as effective B-cell epitopes targeted by neutralizing antibodies for vaccine design.

The seeds of Daucus carota, traditionally used by women in many countries to prevent conception, were proved to have negative impact on reproductive hormone levels as well as on the estrous cycles in albino mice affecting the fertility status. This study is an attempt to investigate the possible role of polyphenols present in the seeds in hampering the reproductive processes. The Molecular Docking, Molecular Dynamics (MD) simulation and binding free energy calculation studies reveal that six polyphenols present in the seeds can bind with the active sites of human Estrogen Receptor (ER) and may interfere in the estrogen signaling in human. These polyphenols were found to bind to a conservative pocket of ER$\alpha$, which is comprised of residues 343–388, 421–428 and 525–540. Docking studies indicated the presence of strong hydrogen bonding, pi–pi interactions and numerous hydrophobic interactions that stabilize the ER$\alpha$-polyphenol complexes.

The docked complexes were further subjected to MM/GBSA analysis to calculate binding free energies. Molecular dynamic simulation studies carried out for a period of 20ns revealed low RMS deviation values suggesting high accuracy of the docking poses and stability of the complexes. Out of the six polyphenols, catechin and epicatechin have shown highest binding affinity towards the ER$\alpha$ receptor. These findings will help in identifying ER modulators of plant origin targeting ER alpha and predicting their effects on the reproductive hormone homeostasis. Moreover, this study may form preliminary basis for further identification of potential herbal antifertility agents.

A long-standing question in molecular biology is whether interfaces of protein-protein complexes are more conserved than the rest of the protein surfaces. Although it has been reported that conservation can be used as an indicator for predicting interaction sites on proteins, there are recent reports stating that the interface regions are only slightly more conserved than the rest of the protein surfaces, with conservation signals not being statistically significant enough for predicting protein-protein binding sites. In order to properly address these controversial reports we have studied a set of 28 well resolved hetero complex structures of proteins that consists of transient and non-transient complexes. The surface positions were classified into four conservation classes and the conservation index of the surface positions was quantitatively analyzed. The results indicate that the surface density of highly conserved positions is significantly higher in the protein-protein interface regions compared with the other regions of the protein surface. However, the average conservation index of the patches in the interface region is not significantly higher compared with other surface regions of the protein structures. This finding demonstrates that the number of conserved residue positions is a more appropriate indicator for predicting protein-protein binding sites than the average conservation index in the interacting region. We have further validated our findings on a set of 59 benchmark complex structures. Furthermore, an analysis of 19 complexes of antigen-antibody interactions shows that there is no conservation of amino acid positions in the interacting regions of these complexes, as expected, with the variable region of the immunoglobulins interacting mostly with the antigens. Interestingly, antigen interacting regions also have a higher number of non-conserved residue positions in the interacting region than the rest of the protein surface.