Here, we present a novel psychrophilic β-glucanase from Glaciozyma antarctica PI12 yeast that has been structurally modeled and analyzed in detail. To our knowledge, this is the first attempt to model a psychrophilic laminarinase from yeast. Because of the low sequence identity (<40%), a threading method was applied to predict a 3D structure of the enzyme using the MODELLER9v12 program. The results of a comparative study using other mesophilic, thermophilic, and hyperthermophilic laminarinases indicated several amino acid substitutions on the surface of psychrophilic laminarinase that totally increased the flexibility of its structure for efficient catalytic reactions at low temperatures. Whereas several structural factors in the overall structure can explain the weak thermal stability, this research suggests that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through existence of longer loops and shorter or broken helices and strands, an increase in the number of aromatic and hydrophobic residues, a reduction in the number of hydrogen bonds and salt bridges, a higher total solvent accessible surface area, and an increase in the exposure of the hydrophobic side chains to the solvent. The results of comparative molecular dynamics simulation and principal component analysis confirmed the above strategies adopted by psychrophilic laminarinase to increase its catalytic efficiency and structural flexibility to be active at cold temperature.
We have investigated computationally the effects of π-conjugation extension on naphtha[2,1-b:6,5-b'] difuran (DPNDF); where we increase the number of fused NDF (central core) and furan rings in the parent molecule. The molecular structures of all analogues have been optimized at the ground (S0) and first excited (S1) states using density functional theory (DFT) and time-dependent density functional theory (TD-DFT), respectively. Then highest occupied molecular orbitals (HOMOs), the lowest unoccupied molecular orbitals (LUMOs), photophysical properties, adiabatic/vertical electron affinities (EAa)/(EAv), adiabatic/vertical ionization potentials (IPa)/(IPv), and hole/electron reorganization energies λh/λe have been investigated. The effect of NDF and furan rings on structural and electro-optical properties has also been studied. Our calculated reorganization energies of 1a, 1b, and 2c reveal them, materials with balanced hole/electron charge transport, whereas 2a and 2b are good hole-transport materials. By increasing the number of furan rings; the photostability was augmented in 2a, 2b, and 2c.
Nonionic surfactants such as the Brij® series are important in the preparation of transdermal drug nanodelivery products using nanoemulsions because of their low toxicity and low irritancy. Here, Monte Carlo (MC) simulation was used to examine the physical behavior of the model deterministic system by using sampling procedures. Metropolis MC simulations were run on three mixtures of two different nonionic surfactants, Brij92 and Brij96, with different compositions in aqueous solution. The system was simulated in the canonical ensemble with constant temperature, volume and number of molecules. Hence, the acceptance ratio for single atom moves of the mixed surfactants increased as the concentration of surfactants increased from 0.494 to 0.591. The lowest total energy for the mixed surfactant systems was -99,039 kcal mol(-1) due to the interaction between all molecules in the system simulated. The physicochemical properties of models such as the radius of gyration and radial distribution function, were also determined. These observations indicate that the behavior and physicochemical of mixed surfactant and PKOEs nanoemulsion systems were described adequately during the simulation.
Escalating demand for sustainable energy resources, because of the rapid exhaustion of conventional energy resources as well as to maintain the environmental level of carbon dioxide (CO2) to avoid its adverse effect on the climate, has led to the exploitation of photovoltaic technology manifold more than ever. In this regard organic materials have attracted great attention on account of demonstrating their potential to harvest solar energy at an affordable rate for photovoltaic technology. 2-vinyl-4,5-dicyanoimidazole (vinazene) is considered as a suitable material over the fullerenes for photovoltaic applications because of its particular chemical and physical nature. In the present study, DFT approaches are employed to provide an exposition of optoelectronic properties of vinazene molecule and molecular crystal. To gain insight into its properties, different forms of exchange correlation energy functional/potential such as LDA, GGA, BLYP, and BL3YP are used. Calculated electronic structure of vinazene molecule has been displayed via HOMO-LUMO isosurfaces, whereas electronic structure of the vinazene molecular crystal, via electronic band structure, is presented. The calculated electronic and optical properties were analyzed and compared as well. Our results endorse vinazene as a suitable material for organic photovoltaic applications.
Design of neutral receptor molecules (ionophores) for beryllium(II) using unsaturated carbonitrile models has been carried out via density functional theory, G3, and G4 calculations. The first part of this work focuses on gas phase binding energies between beryllium(II) and 2-cyano butadiene (2-CN BD), 3-cyano propene (3-CN P), and simpler models with two separate fragments; acrylonitrile and ethylene. Interactions between beryllium(II) and cyano nitrogen and terminal olefin in the models have been examined in terms of geometrical changes, distribution of charge over the entire π-system, and rehybridization of vinyl carbon orbitals. NMR shieldings and vibrational frequencies probed charge centers and strength of interactions. The six-membered cyclic complexes have planar structures with the rehybridized carbon slightly out of plane (16° in 2-CN BD). G3 results show that in 2-CN BD complex participation of vinyl carbon further stabilizes the cyclic adduct by 16.3 kcal mol(-1), whereas, in simpler models, interaction between beryllium(II) and acetonitrile is favorable by 46.4 kcal mol(-1) compared with that of ethylene. The terminal vinyl carbon in 2-CN BD rehybridizes to sp (3) with an increase of 7 % of s character to allow interaction with beryllium(II). G4 calculations show that the Be(II) and 2-CN BD complex is more strongly bound than those with Mg(II) and Ca(II) by 98.5 and 139.2 kcal mol(-1) (-1), respectively. QST2 method shows that the cyclic and acyclic forms of Be(II)-2-CN BD complexes are separated by 12.3 kcal mol(-1) barrier height. Overlap population analysis reveals that Ca(II) can be discriminated based on its tendency to form ionic interaction with the receptor models.
In this work, hybrid functional and G4 methods were employed in the rational design of carbonitrile-carboxaldehyde receptor models for cation recognition. Electron-sharing and ionic interactions between the models and the cations were analyzed utilizing the concepts of overlap population, atomic valence, electrostatic potential, and CHELPG charge in order to elucidate the nature of the heteroatom-metal interaction, the N versus O disparity, and the effect of pH. Receptor fragment models from ionomycin were employed to rationalize the selection of receptor models for discriminating group I cations and enhancing the selectivity for Mg(II) rather than Ca(II), and to examine the effects of keto-enol forms and negatively charged sites. The changes in geometries, overlap population, metal valence, and CHELPG charge upon solvation in heptane medium as compared to the gas phase were negligible. The optimized geometries reveal that the interaction between group II cations and the keto, enol, and enolate forms of 2-cyanoethanal causes 12 % bending of the C-C-N angle from linearity. Overlap populations show that the electron-sharing interaction favors group II cations but that the same mechanism allows Li(I) to compete. The total spin of Li(I) is 17 % greater than that of Ca(II), but the G4 binding energies of the two are separated by more than 50 kcal/mol, favoring group II cations, which may eliminate interference from Li(I). 1,2-Dicyanoethylene, which has only one form, shows similar characteristics. CHELPG analysis shows that Mg(II) transfers 25 and 18 % of its positive charge to 2-cyanoethanal enolate and 1,2-dicyanoethylene, respectively. Hydrogen atoms receive most of the positive charge in both receptors, but the N-termini exhibit strikingly different characteristics. Electrostatic potential contour profiles were found to be in good agreement with the atomic charge distributions. The application of uncharged 1,3-dicarbonyl and 2-cyanocarbonyl receptors and a judicious choice of polymeric membrane that suppresses the Hofmeister effect should lead to high selectivity for magnesium, whereas the utilization of multiple negatively charged ionophores should result in selectivity for calcium.
DFT and G4 results reveal that cations display the following trends in imparting its positive charge to acrylonitrile; H⁺ > Li⁺ > Na⁺ > K⁺ for group I and Be²⁺ > Mg²⁺ > Ca²⁺ for group II. Solvation by water molecules and interaction with cation make the cyano bond more polarized and exhibits ketene-imine character. Bond order in nitrile-cation complexes has been predicted based on the s character of the covalent bond orbitals. Mulliken, CHELPG, and NPA charges are in good agreement in predicting positive charge buildup and GIAO nuclear deshileding on C1. G4 enthalpies show that Mg²⁺ is more strongly bound to acrylonitrile than to acetonitrile by 3 kcal mol⁻¹, and the proton affinity of the former is higher by 0.8 kcal mol⁻¹. G4 enthalpies of reductions support prior experimental observation that metalated conjugated nitriles show enhanced reactivity toward weak nucleophiles to afford Michael addition products.
Fully atomistic molecular dynamics simulation studies of thermotropic bilayers were performed using a set of glycosides namely n-octyl-β-D-glucopyranoside (β-C8Glc), n-octyl-α-D-glucopyranoside (α-C8Glc), n-octyl-β-D-galactopyranoside (β-C8Gal), and n-octyl-α-D-galactopyranoside (α-C8Gal) to investigate the stereochemical relationship of the epimeric/anomeric quartet liner glycolipids with the same octyl chain group. The results showed that, the anomeric stereochemistry or the axial/equatorial orientation of C1-O1 (α/β) is an important factor controlling the area and d-spacing of glycolipid bilayer systems in the thermotropic phase. The head group tilt angle and the chain ordering properties are affected by the anomeric effect. In addition, the L(C) phase of β-C8Gal, is tilting less compared to those in the fluid L(α). The stereochemistry of the C4-epimeric (axial/equatorial) and anomeric (α/β) centers simultaneously influence the inter-molecular hydrogen bond. Thus, the trend in the values of the hydrogen bond for these glycosides is β-C8Gal > α-C8Glc > β-C8Glc > α-C8Gal. The four bilayer systems showed anomalous diffusion behavior with an observed trend for the diffusion coefficients; and this trend is β-C8Gal > β-C8Glc > α-C8Gal > α-C8Glc. The "bent" configuration of the α-anomer results in an increase of the hydrophobic area, chain vibration and chain disorganization. Since thermal energy is dispensed more entropically for the chain region, the overall molecular diffusion decreases.
A novel α-amylase was isolated successfully from Glaciozyma antarctica PI12 using DNA walking and reverse transcription-polymerase chain reaction (RT-PCR) methods. The structure of this psychrophilic α-amylase (AmyPI12) from G. antarctica PI12 has yet to be studied in detail. A 3D model of AmyPI12 was built using a homology modelling approach to search for a suitable template and to generate an optimum target-template alignment, followed by model building using MODELLER9.9. Analysis of the AmyPI12 model revealed the presence of binding sites for a conserved calcium ion (CaI), non-conserved calcium ions (CaII and CaIII) and a sodium ion (Na). Compared with its template-the thermostable α-amylase from Bacillus stearothermophilus (BSTA)-the binding of CaII, CaIII and Na ions in AmyPI12 was observed to be looser, which suggests that the low stability of AmyPI12 allows the protein to work at different temperature scales. The AmyPI12 amino acid sequence and model were compared with thermophilic α-amylases from Bacillus species that provided the highest structural similarities with AmyPI12. These comparative studies will enable identification of possible determinants of cold adaptation.
A theoretical study of a series of five glucose based glycolipid crown ethers and their complexes with Na(+) and K(+) was performed using the density functional theory with B3LYP/6-31 G* to obtain the optimized geometrical structures and electronic properties. The local nucleophilicity of the five molecules was investigated using Fukui function, while the global nucleophilicity was calculated from the ionization potential and electron affinity. The structures and coordination of the complexes were studied to identify the best match of the glycolipid crown ethers with cations. In general, it was found that the oxygen atoms pairs O2 and O3 (or O4 and O6) on the sugar ring are constrained from moving toward the cation, which results in a weaker O-cation coordination strength for the oxygen pair compared to the other oxygen atoms in the crown ether ring. The thermodynamic properties of the binding of the complexes and the exchange reaction in gas phase were evaluated. The cation selectivity pattern among the five molecules was in good agreement with the experiment.
Density functional theory calculations on two glycosides, namely, n-octyl-β-D-glucopyranoside (C(8)O-β-Glc) and n-octyl-β-D-galactopyranoside (C(8)O-β-Gal) were performed for geometry optimization at the B3LYP/6-31G level. Both molecules are stereoisomers (epimers) differing only in the orientation of the hydroxyl group at the C4 position. Thus it is interesting to investigate electronically the effect of the direction (axial/equatorial) of the hydroxyl group at the C4 position. The structure parameters of X-H∙∙∙Y intramolecular hydrogen bonds were analyzed, while the nature of these bonds and the intramolecular interactions were considered using the atoms in molecules (AIM) approach. Natural bond orbital analysis (NBO) was used to determine bond orders, charge and lone pair electrons on each atom and effective non-bonding interactions. We have also reported electronic energy and dipole moment in gas and solution phases. Further, the electronic properties such as the highest occupied molecular orbital, lowest unoccupied molecular orbital, ionization energy, electron affinity, electronic chemical potential, chemical hardness, softness and electrophilicity index, are also presented here for both C(8)O-β-Glc and C(8)O-β-Gal. These results show that, while C(8)O-β-Glc possess- only one hydrogen bond, C(8)O-β-Gal has two intramolecular hydrogen bonds, which further confirms the anomalous stability of the latter in self-assembly phenomena.
5-HT(1A) serotonin and D1 dopamine receptor agonists have been postulated to be able to improve negative and cognitive impairment symptoms of schizophrenia, while partial agonists and antagonists of the D2 and 5-HT(2A) receptors have been reported to be effective in reducing positive symptoms. There is therefore a need for well-defined homology models for the design of more selective antipsychotic agents, since no three-dimensional (3D) crystal structures of these receptors are currently available. In this study, homology models were built based on the high-resolution crystal structure of the β(2)-adrenergic receptor (2RH1) and further refined via molecular dynamics simulations in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer system with the GROMOS96 53A6 united atom force field. Docking evaluations with representative agonists and antagonists using AutoDock 4.2 revealed binding modes in agreement with experimentally determined site-directed mutagenesis data and significant correlations between the computed and experimental pK (i) values. The models are also able to distinguish between antipsychotic agents with different selectivities and binding affinities for the four receptors, as well as to differentiate active compounds from decoys. Hence, these human 5-HT(1A), 5-HT(2A), D1 and D2 receptor homology models are capable of predicting the activities of novel ligands, and can be used as 3D templates for antipsychotic drug design and discovery.
A molecular docking tool of AutoDock3.05 was evaluated for its ability to reproduce experimentally determined affinities of various sialic acid analogues toward hemagglutinin of influenza A virus. With the exception of those with a C6-modified glycerol side chain, the experimental binding affinities of most sialic acid analogues (C2, C4 and C5-substituted) determined by viral hemadsorption inhibition assay, hemagglutination inhibition assay and nuclear magnetic resonance correlated well with the computationally estimated free energy of binding. Sialic acid analogues with modified glycerol side chains showed only poor correlation between the experimentally determined hemagglutinin inhibitor affinities and AutoDock3.05 scores, suggesting high mobility of the glutamic acid side chain at the glycerol binding pocket, which is difficult to simulate using a flexi-rigid molecular docking approach. In conclusion, except for some glycerol-substituted sialic acid analogues, the results showed the effectiveness of AutoDock3.05 searching and scoring functions in estimating affinities of sialic acid analogues toward influenza A hemagglutinin, making it a reliable tool for screening a database of virtually designed sialic acid analogues for hemagglutinin inhibitors.
In this study fragment-based drug design is combined with molecular docking simulation technique, to design databases of virtual sialic acid (SA) analogues with new substitutions at C2, C5 and C6 positions of SA scaffold. Using spaces occupied by C2, C5 and C6 natural moieties of SA when bound to hemagglutinin (HA) crystallographic structure, new fragments that are commercially available were docked independently in all the pockets. The oriented fragments were then connected to the SA scaffold with or without incorporation of linker molecules. The completed analogues were docked to the whole SA binding site to estimate their binding conformations and affinities, generating three databases of HA-bound SA analogues. Selected new analogues showed higher estimated affinities than the natural SA when tested against H3N2, H5N1 and H1N1 subtypes of influenza A. An improvement in the binding energies indicates that fragment-based drug design when combined with molecular docking simulation is capable to produce virtual analogues that can become lead compound candidates for anti-flu drug discovery program.
The effect of organic solvent on the structure and dynamics of proteins was investigated by multiple molecular dynamics simulations (1 ns each) of Candida rugosa lipase in water and in carbon tetrachloride. The choice of solvent had only a minor structural effect. For both solvents the open and the closed conformation of the lipase were near to their experimental X-ray structures (C(alpha) rms deviation 1-1.3 A). However, the solvents had a highly specific effect on the flexibility of solvent-exposed side chains: polar side chains were more flexible in water, but less flexible in organic solvent. In contrast, hydrophobic residues were more flexible in organic solvent, but less flexible in water. As a major effect solvent changed the dynamics of the lid, a mobile element involved in activation of the lipase, which fluctuated as a rigid body about its average position. While in water the deviations were about 1.6 A, organic solvent reduced flexibility to 0.9 A. This increase rigidity was caused by two salt bridges (Lys85-Asp284, Lys75-Asp79) and a stable hydrogen bond (Lys75-Asn 292) in organic solvent. Thus, organic solvents stabilize the lid but render the side chains in the hydrophobic substrate-binding site more mobile. [figure: see text]. Superimposition of open (black, PDB entry 1CRL) and closed (gray, PDB entry 1TRH) conformers of C. rugosa lipase. The mobile lid is indicated.
This report present the results of natural energy decomposition analysis (NEDA), natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM) calculations of three derivatives of biphenyl-1-aza-18-crown-6 ether and their 1:1 complexes with Cd(2+). All calculations used the B3LYP density functional theory in combination with the 6-311G and WTBS basis sets for ligands and Cd(2+) ion, respectively. Ligands 1 and 3 have a single 1-aza-18-crown-6, substituent; ligand 2 has two such substituents. The results show that, in the optimized geometries of the complexes, the distance between N and Cd(2+) is greater than the distance between O and Cd(2+). NBO and QTAIM data confirm these results. There was no stabilization energy or bond critical point for N · · · Cd(2+) in NBO or QTAIM, respectively. Data show that the O · · · Cd(2+) interaction is a kind of closed shell interaction. The trend of the calculated stabilization energy was similar to the experimental data. Different contributions of interaction energies for complex formation were analyzed by NEDA, and the results show that the main component of the interactions is accounted for by polarization.
The present study spotlights the designing of new derivatives of 2,7-bis (4-octylphenyl) naphtho [2,1-b:6,5-b'] difuran (C8-DPNDF) by substituting the alkyl groups (methyl, ethyl, propyl, butyl, pentyl, hexyl, and heptyl groups) at para position. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) methods are employed to optimize the molecular structures in ground and first excited states, respectively. Several electro-optical properties including hole/electron reorganization energies (λh/λe), electron affinities (EAs), ionization potentials (IPs), molecular electrostatic potentials (MEP), and frontier molecular orbitals (FMOs) have been evaluated. Furthermore their transfer integrals and intrinsic mobilities values have also been calculated. From this study, it is found that hole mobility of octyl containing derivative is raised to 4.69 cm(2) V(-1) s(-1). Moreover with attaching octyl group, hole transfer integral values have also been enhanced in newly designed derivatives. The balanced hole and electron reorganization energies, and improved transfer integrals lead to enhanced mobility in derivatives with octyl group, highlighting them as an efficient hole transfer material. Unlike the other electro-optical properties, the intrinsic hole mobility has increased because of transfer integral values of octyl containing derivative C8-DPNDF due to the dense and close crystal packing of C8-DPNDF. However, photostability of furan-based materials has not changed by increasing length of extended alkyl chain. Thus our present investigation highlights the importance of alkyl auxiliary groups that are often neglected/replaced with simple methyl group to save computation costs. Graphical Abstract The hole and electron reorganization energies of naphtho[2,1-b:6,5-b']difuran derivatives.
The sigma-E transcription factor (σETF) can be found in most of the bacteria cells including Bacillus thuringiensis. However, the cellular regulatory mechanisms of these transcription factors in the mass production of δ-endotoxins during sporulation stage are yet to be revealed. In addition, the recognition of DNA towards σETF DNA binding motifs that led to the transcription activities is also being poorly studied. Therefore, this work studied the possible DNA binding motifs of σETF by utilising in silico approaches. The structure of σETF was first built via three different computational methods. A cognate DNA sequence was then docked to the predicted σETF DNA-binding motifs. The binding free energy calculated using molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) for triplicate 50 ns simulation of σETF-DNA complex revealed favourable binding energy of DNA to σETF (average ∆Gbind = -34.57 kcal/mol) mainly driven by non-polar interactions. This study revealed that σETF LYS131, ARG133, PHE138, TRP146, ARG222, LYS225 and ARG226 are most likely the key residues upon the binding and recognition of DNA prior to transcription actives. Since determination of genome-regulating protein which recognises specific DNA sequence is important to discriminate between the proteins preferences for different genes, this study might provide some understanding on the possible σETF-DNA recognition prior to transcription initiated for the δ-endotoxins production.
Fruit bromelain is a cysteine protease accumulated in pineapple fruits. This proteolytic enzyme has received high demand for industrial and therapeutic applications. In this study, fruit bromelain sequences QIM61759, QIM61760 and QIM61761 were retrieved from the National Center for Biotechnology Information (NCBI) Genbank Database. The tertiary structure of fruit bromelain QIM61759, QIM61760 and QIM61761 was generated by using MODELLER. The result revealed that the local stereochemical quality of the generated models was improved by using multiple templates during modelling process. Moreover, by comparing with the available papain model, structural analysis provides an insight on how pro-peptide functions as a scaffold in fruit bromelain folding and contributing to inactivation of mature protein. The structural analysis also disclosed the similarities and differences between these models. Lastly, thermal stability of fruit bromelain was studied. Molecular dynamics simulation of fruit bromelain structures at several selected temperatures demonstrated how fruit bromelain responds to elevation of temperature.
Some important optoelectronic properties of naphtho[2,1-b:6,5-b']difuran (DPNDF) and its two derivatives have been limelighted by applying the density functional theory (DFT). Due to their low cost, high stability and earth abundance, the DPNDF and its derivatives are considered as potential organic semiconductor materials for their optoelectronics applications. Highly proficient derivatives are obtained systematically by attaching -CN (cyanide) to DPNDF at various sites. Our calculations indicate that DPNDF has a wide and direct band gap with an energy gap of 3.157 eV. Whereas the band gaps of its derivatives are found to be decreased by 88 meV for derivative "a" and 300 meV for derivative "b" as a consequence of p orbitals present in C and N atoms in derivative structures. The narrowing of the energy gap and density of states for the derivatives of DPNDF in the present investigation suggest that energy gap can be engineered for desirable optoelectronic applications via derivatives designing. Furthermore, their obtained results for optical parameters such as the dielectric and conductivity functions, reflectivity, refractive index, and the extinction coefficients endorses their aptness for optoelectronic applications. Graphical Abstract Real part of dielectric function for derivative "b".