Crystallization of CaCO3 in the presence of sulfate and additives: experimental and molecular dynamics simulation studies

The effects of sulfate and BHTPMP (Bis (hexamethylene) triaminepentakis (methylene phosphonic acid)) on the crystallization rate, phase composition and morphology of calcium carbonate have been studied. It was observed that sulfate reduces the nucleation rate and favors the formation of aragonite form in the calcium carbonate precipitate. Moreover, in the presence of sulfate the rhombohedral morphology of the calcite crystals is modified, and during the formation of calcite, the development of {104} faces are more significantly prohibited than {110} faces. In the presence of sulfate together with BHTPMP, the crystallization process is inhibited and the modified morphology and the dominant calcite form are observed in the solid. The results from molecular dynamics simulations show the more strong combination of sulfate with calcite surface, in particular the {104} face, in comparison with the aragonite surface. The strong interaction of BHTPMP with sulfate and the aragonite surface favors the formation of the dominant calcite phase in the precipitate.     

Molecular simulation studies of protein interactions with zwitterionic phosphorylcholine self-assembled monolayers in the presence of water

Molecular simulations were performed to study the interactions between a protein (lysozyme, LYZ) and phosphorylcholine-terminated self-assembled monolayers (PC-SAMs) in the presence of explicit water molecules and ions. The results show that the water molecules above the PC-SAM surface create a strong repulsive force on the protein as it approaches the surface. The structural and dynamic properties of the water molecules above the PC-SAM surface were analyzed to provide information regarding the role of hydration in surface resistance to protein adsorption. It can be seen from residence time dynamics that the water molecules immediately above the PC-SAM surface are significantly slowed down as compared to bulk water, suggesting that the PC-SAM surface generates a tightly bound, structured water layer around its head groups. Moreover, the orientational distribution and reorientational dynamics of the interfacial water molecules near the PC-SAM surface were found to have the ionic solvation nature of the PC head groups. These properties were also compared to those obtained previously for an oligo(ethylene glycol) (OEG) SAM system and bulk water.     

Molecular docking and 3D-QSAR studies on the glucocorticoid receptor antagonistic activity of hydroxylated polychlorinated biphenyls

The glucocorticoid receptor (GR) antagonistic activities of hydroxylated polychlorinated biphenyls (HO-PCBs) were recently characterised. To further explore the interactions between HO-PCBs and the GR, and to elucidate structural characteristics that influence the GR antagonistic activity of HO-PCBs, molecular docking and three-dimensional quantitative structure–activity relationship (3D-QSAR) studies were performed. Comparative molecular similarity indices analysis (CoMSIA) was performed using both ligand- and receptor-based alignment schemes. Results generated from the receptor-based model were found to be more satisfactory, with q² of 0.632 and r² of 0.931 compared with those from the ligand-based model. Some internal validation strategies (e.g. cross-validation analysis, bootstrapping analysis and Y-randomisation) and an external validation method were used respectively to further assess the stability and predictive ability of the derived model. Graphical interpretation of the model provided some insights into the structural features that affected the GR antagonistic activity of HO-PCBs. Molecular docking studies revealed that some key residues were critical for ligand–receptor interactions by forming hydrogen bonds (Glu540) and hydrophobic interactions with ligands (Ile539, Val543 and Trp577). Although CoMSIA sometimes depends on the alignment of the molecules, the information provided is beneficial for predicting the GR antagonistic activities of HO-PCB homologues and is helpful for understanding the binding mechanisms of HO-PCBs to GR.     

Atom-based 3D-QSAR,molecular docking,DFT, and simulation studies of acylhydrazone,hydrazine, and diazene derivatives as IN-LEDGF/p75 inhibitors

Structural Chemistry - Since HIV-1 integrase makes use of host genome machinery to accomplish the replication process, where LEDGF/p75 (a cellular cofactor) executes in the lentiviral integration...     

Clouding phenomenon and SANS studies on tetra-n-butylammonium dodecylsulfate micellar solutions in the absence and presence of salts

Clouding phenomenon in aqueous micellar solutions of an anionic surfactant tetra-n-butylammonium dodecylsulfate (TBADS) has been observed as a function of surfactant concentration. Small-angle neutron scattering (SANS) experiments in these systems show clustering of micelles as the temperature approaches the cloud point (CP). The individual micelles and the clusters of micelles coexist at CP. The clustering of micelles depends on the surfactant concentration and temperature. It is proposed that clustering is due to depletion of H-bonded water present around the butyl chains at the micellar surface. This is associated with entropy gain which is considered to be the major thermodynamic factor related to micellar aggregation. The structures (clusters) that emerge depend on the relative lengths of the alkyl chains of the counterion and can be tuned by the temperature.     

Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: molecular docking and 3D QSAR studies

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is as an attractive target for the development of novel antitrypanosomatid agents. In the present work, comparative molecular field analysis and comparative molecular similarity index analysis were conducted on a large series of selective inhibitors of trypanosomatid GAPDH. Four statistically significant models were obtained ( r2 > 0.90 and q2 > 0.70), indicating their predictive ability for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values were in good agreement with the experimental results. Molecular modeling studies provided further insight into the structural basis for selective inhibition of trypanosomatid GAPDH.     

Molecular evolution of the plant ECERIFERUM1 and ECERIFERUM3 genes involved in aliphatic hydrocarbon production

The Arabidopsis ECERIFERUM1 (CER1) protein is a decarbonylase that converts fatty acid metabolites into alkanes. Alkanes are components of waxes in the plant cuticle, a waterproof barrier serving to protect land plants from both biotic and abiotic stimuli. CER1 enzymes can be used to produce alternative and sustainable hydrocarbons in eukaryotic systems. In this report we identified 193 CER1 and 128 CER3 sequences from 56 land plants respectively. CER1 and CER3 proteins have high amino acid similarity and both are involved in alkane synthesis in Arabidopsis. The common homologues of CER1 and CER3 genes were identified in three species of chlorophytes, which may be one of the earliest plant taxa that possess CER1 and CER3 genes. To facilitate potential applications, the 3-dimensional structure and conserved motifs of CER1 proteins were also characterized. CER1 and CER3 proteins are structurally similar, but CER1 proteins have more conserved histidine-containing motifs common to fatty acid hydroxylases and stearoyl-CoA desaturases. There was no significant loss or gain of protein motifs after ancient and recent duplications, suggesting that varied properties of CER1 proteins may be associated with less-conserved regions. Among 56 land plants, the codon-based assessments of selection modes revealed that neither entire proteins nor individual amino acids of CER1 proteins were significantly subjected to positive selection, indicating that CER1 proteins are highly conserved throughout evolution.     

Antimicrobial activities of 1-phenyl-3-methyl-4-trichloroacetyl-pyrazolone: Experimental,DFT studies,and molecular docking investigation

The rate of bacterial resistance to antibiotics is faster than the rate of discovery of new antibiotic classes. However, development of novel compounds with similar behavior but with a better therapeutic action has posed a serious challenge to researchers. Therefore, discovering of new novel drugs is of great importance in combating health problems and improving the quality of human life. In this research, first principle density functional theory (DFT) along with molecular docking approach were utilized for the investigation of 1-phenyl-3-methyl-4-trichloroacetyl-pyrazolone-5 (HTcP) to address some factors that are linked to this phenomenon. The theoretical computations were carried out utilizing the Becke-3-Parameter-hybrid model of Lee-Yang-Parr (B3LYP) with the 6-31+G (d, p) basis set. The most active site of the studied compound was studied within the framework of molecular electrostatic potential (ESP) meanwhile the strength and nature of the bond was studied using quantum theory of atoms in molecules (QTAIM). The antibacterial activities of the title structure was tested in this study using three proteins, 4YNT, 4YNU, and 5UZ9, with the help of Bio – via discovery studio and Auto dock vina tool via molecular docking simulations. The compound had a higher binding energy with the 4YNT and 4YNU proteins (?7.7 kcal/mol). Also controlled model was used in the docking analysis which shows no much significant different between the modelled structure and the commercial drug Kanamycin. In addition, a computer simulation was used to predict the absorption, distribution, metabolism, excretion, and toxicity profiles of the compound under investigation (ADMET). The result obtained from the ADMET studies indicated that the structure under study has moderate antibacterial activities.     

Molecular modeling of A1 and A2A adenosine receptors: comparison of rhodopsin- and beta2-adrenergic-based homology models through the docking studies

Adenosine receptors (ARs) are members of the superfamily of G protein-coupled receptors. The homology models of adenosine A1 and A2A receptors were constructed. The high-resolution X-ray structure of bovine rhodopsin and crystal structure of beta2-adrenergic receptor were used as templates. The binding sites of the A1 and A2A ARs were constructed by using data obtained from mutagenesis experiments as well as docking simulations of the respective AR antagonsists DPCPX and XAC. To compare rhodopsin- and beta2-adrenergic-based models, the binding mode of A1 (KW-3902, LUF-5437) and A2A (KW-6002, ZM-241385) ARs antagonists were also examined. The differences in the binding ability of both models were noted during the study. The beta2-adrenergic-based A2A AR model was much more capable to stabilize the ligand in the binding site cavity than the corresponding rhodopsin-based A2A AR model, however, such differences were not so clear in case of A1 AR models. It was suggested that for the A1 AR it is possible to use the crystal structure of rhodopsin as a template as well as beta2-adrenergic receptor, but for A2A AR, with the now available beta2-adrenergic receptor X-ray structure, docking studies should be avoided on the rhodopsin-based model. However, taking into account that the beta2AR shares about 31% of the residues with the AR in comparison to 21% in case of bRho, we suggest using beta2-adrenergic-based models for the A1 and A2A ARs for further in silico ligand screening also because of their generally better ability to stabilize ligands inside the binding pocket.     

3D-QSAR,molecular docking and in silico ADMET studies of propiophenone derivatives with anti-HIV-1 protease activity

Structural Chemistry - HIV protease inhibitors are one of the most important agents for the treatment of HIV infection. In this work, molecular modeling studies combining 3D-QSAR, molecular...     

A hydrodynamic study of the retention of polyethylene glycols by cellulose acetate membranes in the absence and presence of proteins

The ultrafiltration behaviour of polyethylene glycols has been investigated with respect to their partial retention by YM5 and YM10 membranes. Retention coefficients were found to follow a log-normal distribution except at low molecular weights, which exhibited higher than expected values. Increasing the applied pressure resulted in increased retention of PEG, although linear flux-pressure relationships were observed in all cases. Increasing hydrodynamic activity by applying higher stirrer speeds led to reduced permeate concentrations. The mean molecular weights of the permeates were higher under hydrodynamic conditions resulting in lower retention coefficients, which suggests increased permeabilities for the larger PEG component molecules.

The retention behaviour of solutions of PEG with varying concentration of bovine serum albumin (BSA) as the flux rate was altered paralleled the results for pure PEG solutions. However, when the flux rate was kept constant and the concentration varied, there was an initial increase of retention at a BSA concentration of 0.2% w/v and thereafter a reduction up to a tested bulk concentration of 10%. Various proposals were made to explain this behaviour.     

The effects of single-walled carbon nanotubes (SWCNTs) on the structure and function of human serum albumin (HSA): Molecular docking and molecular dynamics simulation studies

Here, the interaction of single-walled carbon nanotubes (SWCNTs) and human serum albumin (HSA) as one of the most important proteins for carrying and binding of drugs was investigated and the impact of radius to volume ratio and chirality of the SWCNTs was evaluated using molecular docking method. Molecular docking results represented that zigzag SWCNT with radius to volume ratio equal to 6.77 × 10^?3 Å^?2 has the most negative binding energy (?17.16 kcal mol^?1) and binds to the HSA cleft by four π–cation interactions. To study the changes of HSA structure, the complex of HSA–SWCNT was subjected to 30 ns molecular dynamics simulation. The MD results showed that HSA was compressed about 2% after interaction with SWCNT. The equilibrated structure of HSA–SWCNT complex was used to compare the binding of warfarin to HSA in the absence and presence of SWCNT. The obtained results represent that warfarin-binding site was changed in the presence of SWCNT and its binding energy was increased. Really, warfarin was bound on the surface of SWCNT instead of its binding site on HSA. It means that HSA function as a carrier for warfarin is altered, the free concentration of warfarin is changed, and its release is decreased in the presence of SWCNT.     

3D-QSAR and docking studies of selective GSK-3beta inhibitors. Comparison with a thieno[2,3-b]pyrrolizinone derivative, a new potential lead for GSK-3beta ligands

The three-dimensional structures of 3-anilino-4-arylmaleimides, selective GSK-3beta inhibitors, were correlated to their biological affinities by 3D-QSAR studies (CoMFA method). The cocrystallographic data of GSK-3beta vs 3-anilino-4-arylmaleimide allowed us to compare 3D-QSAR results to experimental intermolecular interactions. The results of the CoMFA analysis did not really correspond to the interactions recorded in the active site, but they characterized fundamental features (areas of the active site) of the interactions ligand-receptor. These studies were the starting point to analyze a new GSK-3beta ligand, a thieno[2,3-b]pyrrolizinone derivative. This comparison based on docking and simulation approaches allowed us to confirm one preferential orientation of this ligand inside the active site, explaining the relationship with the reference 3-anilino-4-arylmaleimide derivatives and its biological affinity.     

Molecular structural investigations of quinoxaline derivatives through 3D-QSAR,molecular docking,ADME prediction and pharmacophore modeling studies for the search of novel antimalarial agent

In the present article, a dataset of 63 quinoxaline derivatives were taken for antimalarial activity and pharmacophore were developed. Atom based method was used to develop a three dimensional quantitative structure activity relationship (3D-QSAR) model. On comparison of all statistical parameters, model AHRRR23 was found to be the most effective and predictive QSAR model as it satisfied all statistical parameters of a good model. The model AHRRR23 showed an adequate R² value for the training set 0.9446, good predictive power with Q² of 0.6409, good F- value, low SD 0.1218 value and outstanding Pearson-R values and low RMSE 0.2779 values of the model. The docking studies also gives very good results with good RMSD values. 3D QSAR, docking and ADME studies exhibits that the developed model could be employed as a potential lead for further study as antimalarial drug.     

Binding behaviour and conformational properties of globular proteins in the presence of immobilised non-polar ligands used in reversed-phase liquid chromatography

The thermodynamic and extra-thermodynamic dependencies of five types of cytochrome c in water-acetonitrile mixtures of different composition in the presence of immobilised n-octyl ligands as a function of temperature from 278 K to 338 K have been investigated. The corresponding enthalpic, entropic and heat capacity parameters, deltaHdegrees assoc, deltaS degrees assoc and delta C degrees p, have been evaluated from the observed non-linear Van't Hoff plots of these globular proteins in these heterogeneous systems. The relationships between the free energy dependencies, various molecular parameters and extra-thermodynamic dependencies (empirical correlations) of these protein-non-polar ligand interactions have also been examined. Thus, the involvement of enthalpy-entropy compensation effects has been documented for the binding of these cytochrome cs to solvated n-octyl ligands. Moreover, the results confirm that this experimental approach permits changes in molecular surface area due to the unfolding of these proteins on association with non-polar ligands as a function of temperature to be correlated with other biophysical properties. This study thus provides a general procedure whereby the corresponding free energy dependencies of globular proteins on association with solvated non-polar ligands in heterogeneous two-phase systems can be quantitatively evaluated in terms of fundamental molecular parameters.