Interaction Energy Profiles Research Articles

Electrostatic interactions between soft nanoparticles beyond the Derjaguin approximation: Effects of finite size of ions and charges, dielectric decrement and ion correlations

HypothesisElectrostatic interactions between colloids are governed by the overlap of their electric double layers (EDLs) and the ionic screening of the structural charges distributed at their core surface and/or in their peripheral ion-permeable shell, relevant to soft particles like polymer colloids and microorganisms. Whereas ion size-mediated effects on the organization of isolated EDLs have been analysed, their contribution to the electrostatic energy of interacting soft particles has received less attention Theory and simulationsHerein, we elaborate a formalism to evaluate the electrostatic interaction energy profile between spherical core/shell particles, building upon a recent Poisson-Boltzmann theory corrected for the sizes of ions and particle structural charges, for ion correlations and dielectric decrement. Interaction energy is derived from pairwise disjoining pressure and exact Surface Element Integration method, beyond the Derjaguin approximation. The theory is sufficiently flexible to tackle homo- and hetero-interactions that involve weakly to highly charged hard, porous or core/shell nano- to micro-sized particles in asymmetric multivalent electrolytes. FindingsResults illustrate how ion steric effects, ion correlations and dielectric decrement impact the sign, magnitude and range of the interactions depending on the particle size, the Debye length, and the geometric and electrostatic properties of the particle core and shell components.

A journey in unraveling the enantiorecognition mechanism of 3,5-dinitrobenzoyl-amino acids with two Cinchona alkaloid-based chiral stationary phases: The power of molecular dynamic simulations

BackgroundInnovations in computer hardware and software capabilities have paved the way for advances in molecular modelling techniques and methods, leading to an unprecedented expansion of their potential applications. In contrast to the docking technique, which usually identifies the most stable selector-selectand (SO-SA) complex for each enantiomer, the molecular dynamics (MD) technique enables the consideration of a distribution of the SO-SA complexes based on their energy profile. This approach provides a more truthful representation of the processes occurring within the column. However, benchmark procedures and focused guidelines for computational treatment of enantioselectivity at the molecular level are still missing. ResultsTwenty-eight molecular dynamics simulations were performed to study the enantiorecognition mechanisms of seven N-3,5-dinitrobenzoylated α- and β-amino acids (DNB-AAs), occurring with the two quinine- and quinidine-based (QN-AX and QD-AX) chiral stationary phases (CSPs), under polar-ionic conditions. The MD protocol was optimized in terms of box size, simulation run time, and frame recording frequency. Subsequently, all the trajectories were analyzed by calculating both the type and amount of the interactions engaged by the selectands (SAs) with the two chiral selectors (SOs), as well as the conformational and interaction energy profiles of the formed SA-SO associates. All the MDs were in strict agreement with the experimental enantiomeric elution order and allowed to establish (i) that salt-bridge and H-bond interactions play a pivotal role in the enantiorecognition mechanisms, and (ii) that the π-cation and π-π interactions are the discriminant chemical features between the two SOs in ruling the chiral recognition mechanism. SignificanceThe results of this work clearly demonstrate the high contribution given by MD simulations in the comprehension of the enantiorecognition mechanism with Cinchona alkaloid-based CSPs. However, from this research endeavor it clearly emerged that the MD protocol optimization is crucial for the quality of the produced results.

Dual roles of goethite coating on the transport of plastic nanoparticles in heterogeneous porous media: The significance of collector surface roughness

This study systematically examines the roles of positive goethite on the retention and release of negative plastic nanoparticles (PSNPs) with different surface functional groups (Blank, -COOH, and -NH2). It provides the first evidence for the dual roles of goethite coatings on colloid transport; e.g., increased transport caused by surface morphology modification or decreased transport due to increased surface roughness and charge heterogeneity. Although previous work has shown that goethite-coated sand increases the retention of negative colloids, this work demonstrates that collector surface roughness can also reduce the retention of PSNPs due to increased interaction energy profiles. Nonmonotonic retention of all the different functionalized PSNPs was observed in goethite-coated rough sand, and the magnitude of variations was contingent on the PSNP functionalization, the solution ionic strength (IS), and the goethite coating. The release of PSNPs with IS decrease (phase I) and pH increase (phase II) varied significantly due to differences in energy barriers to detachment, e.g., release in phase I was inhibited in both goethite-coated sands, whereas release in phase II was enhanced in coated smooth sand but completely inhibited in rough sand. The findings of this study provide innovative insight into transport mechanisms for colloidal and colloid-associated contaminants.

Towards understanding hybrid influencing mechanisms of substrate microstructure on SERS effect

Micro/nano hierarchical structures have been investigated as a manner to improve the enhancement factor of surface enhanced Raman scattering (SERS). However, the exploration of influencing mechanisms of substrate microstructure on SERS effect is relatively lacking at present. In this study, finite element analysis (FEA) and molecular dynamics (MD) simulations were conducted, aiming to reveal the intrinsic relationships between microstructure characterization and Raman signal intensity. The distributions of near field and far field, as well as the energy density on substrate surfaces with various microstructures were obtained, and their influencing mechanisms on electromagnetic enhancement (EM) and chemical enhancement (CM) were analyzed. Meanwhile, the adsorption capacity of probe molecule on different substrate was expounded from the perspectives of superficial area, interaction energy and surface profile characteristics. Results demonstrated that the characterization parameter S/d × h, of which S, d and h are respectively the superficial area, interval space of adjacent micro-cavities and peak-valley height of surface microstructure, significantly determines the electric enhancement factor of electric field intensity and the energy density at the same time. The substrate surface with larger superficial areas can generate higher interaction energy thereby more probe molecules can be caught successfully. In addition, the molecular clusters are easier to form near convexities compared with the concaves on the same substrate. What was studied in this work is expected to provide a theoretical reference for the structural optimization of SERS substrate with high performances.

Exploring the Reactivity of Donor-Acceptor Systems through a Combined Conceptual and Constrained DFT Approach.

In the context of the conceptual density functional theory (cDFT) and based on the computational efficiency of the constrained DFT (CDFT), we demonstrate that chemical reactivity can be governed by the difference between the local interacting chemical potentials of the reactants (referred as Edual), in agreement with Sanderson's equalization principle. In a proof-of-concept study, we investigated illustrative examples involving typical non-covalent donor-acceptor systems and reactive systems are provided. For the selected systems, our approach reveals significant mimicking between Edual and the DFT-computed intermolecular interaction energy profiles. We further evaluate the influence of the Coulomb and exchange-correlation contributions in Edual. These latter results suggest that numerous potential energy surfaces of clusters can be explored using a Sanderson-like model only based on classical interactions between molecular orbitals domains. To conclude, this study achieved a deeper understanding of the principles of cDFT and assessed, in a wider context, its efficiency in predicting the chemical reactivity.

Nitric acid oxidation and urea modification of carbon fibres as biofilm carriers

ABSTRACT Carbon fibres (CF) are commonly used as carriers in biofilm-based wastewater treatment. The surface properties of the CF are herein modified using a combination of nitric acid oxidation and urea to optimise the carrier to immobilise bacterial cells. The capacity of the CF carriers to immobilise bacterial cells and activated sludge is evaluated using bacterial cell adhesion and sludge immobilisation tests. The total interaction energy profiles between the CF supports and bacterial cells were calculated according to the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory to explain the mechanism by which these modifications enhance this immobilisation capacity. CF-U has a high capacity for immobilising bacterial cells and activated sludge (3.7 g-sludge/g-CF supports) owing to its low total interaction energy. Nitric acid oxidation reduced the diiodomethane contact angle of CF from 55.1° to 38.5°, which reduced the Lifshitz-van der Waals interaction energy, while urea modification further increased the zeta potential of CF from 12.8 mV to −0.7 mV, thereby reducing the electrostatic interaction energy. Experiments and DLVO theory both determined that a combination of nitric acid oxidation and urea modification significantly enhanced the ability of CF to immobilise microorganisms.

Effect of surfactant compounding on the wettability of talcum powder

AbstractTalcum powder is one of the leading causes of pneumoconiosis, adding compound surfactants to the dust removal process can significantly increase the effectiveness of the dust removal. Therefore, it is of great significance to study the effect of compound surfactants on the wettability of talcum powder. This paper focuses on the ability of compound surfactants to increase the wettability of talcum powder surface by using Materials Studio 8.0. The simulation results were analyzed from the water adsorbed amount, interaction energy, and water molecule concentration profile. Combined with the experimental data of contact angle, the optimal surfactant compounding method was obtained. The simulation results revealed that stable adsorption structures can be formed by the compound of anionic and nonionic surfactants, which can reduce the electrostatic repulsion between anionic surfactants effectively and promote the directional arrangement of nonionic surfactants on the talcum powder surface. When the molar ratio of sodium dodecyl sulfate (SDS) and Polysorbate 80 was 0.4:0.6, the amount of absorbed water reached 113, which is better than monomers and other compound surfactants. The contact angle experiment results indicated a consistent variation law with the simulation results. The contact angle decreased from 68.48° to 19.84° using the compounding method mentioned above, which has the optimum wetting effect among the four compounding methods. The research results will provide a reference for the application of compound surfactants in talcum powder dustproof work.

Nano-SiO2 transport and retention in saturated porous medium: Influence of pH, ionic strength, and natural organics

Nano silica (nSiO2), induces potential harmful effects on the living environment and human health. It is well established that SiO2 facilitates the co-transport of a variety of other contaminants, including heavy metals and pesticides. The current study focused on the systematic evaluation of the effects of multiple physicochemical parameters such as pH (5, 7, and 9), ionic strength (10, 50, and 100 mM), and humic acid (0.1, 1, and 10 mg/L) on the transport and retention of nSiO2 in saturated porous medium. Additionally, the influent concentration of nSiO2 (10, 50, and 100 mg/L) was also varied. Our experimental findings indicate that the size of nSiO2 aggregates was directly related to the pH, ionic strength, HA, and particle concentration had a significant impact on the breakthrough curves (BTCs). The stability provided by the varying concentrations of pH and humic acid had a significant effect on the size of nSiO2 aggregates and transport (C/C0 > 0.7). The presence of a greater magnitude of negative charge on the surface of both nSiO2 and quartz sand resulted in less aggregation and enhanced flow of nSiO2 through the sand column. The Electrostatic and steric repulsion forces were the primary governing mechanisms in relation to the size of nSiO2 aggregates, affecting the single-collector efficiency and attachment efficiency, which determined the maximal transport of nSiO2. Conversely, a probable increase in Van der Waals force of attraction exacerbated the particle deposition and reduced their mobility for high ionic strength, and particle concentrations (C/C0 < 0.1). The formation of large nSiO2 aggregates, in particular, was principally responsible for the enhancement of nSiO2 retention in sand columns over a broad range of IS and particle concentration. The interaction energy profiles based on the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory were determined to understand the mechanism of nSiO2 deposition. Aditionally, all the experimental BTCs were mathematically simulated and justified by the colloidal filtration theory (CFT). Considering the environmental ramifications, the transport behavior of nSiO2 was further evaluated in various natural matrices such as river, lake, ground, and tap water. The nSiO2 suspended in the river, lake, and tap water had significantly higher mobility (C/C0 > 0.7), whereas groundwater indicated higher retention (C/C0 < 0.3). The study advances our collective knowledge of physicochemical and environmental parameters that can affect particle mobility.

The effects of pH, ionic strength, and natural organics on the transport properties of carbon nanotubes in saturated porous medium

Carbon Nanotubes (CNTs) are widely utilized, and their inadvertent release into the soil and ground water systems may have detrimental environmental implications. Therefore, it is critical to comprehend the effect of several environmental conditions on the fate and transport of CNTs in porous media. In previous studies, a narrow range of pH, ionic strength, and collector grain size have only been considered while evaluating the transport and retention of functionalized multiwalled carbon nanotubes (f-MWCNTs). None have highlighted the effect of environmentally relevant concentrations of natural organic matter and particle concentrations on the mobility of f-MWCNTs in porous medium. The current study aims to fill the knowledge gap by evaluating the fate and transport of f-MWCNTs at different, environmentally relevant physicochemical conditions of pH (5, 7, and 9), ionic strengths (10, 50, and 100 mM), humic acid as representative of natural organic matter (0.1, 1, and 10 mg/L) and particle concentrations (10, 25, and 50 mg/L) through saturated porous medium (quartz sand). It was noted that a wide range of pH and humic acid imparted an overall negative charge on the particles, enhancing their mobility (C/C0 > 0.8). However, transport of the f-MWCNTs was hindered in the presence of high ionic strength and particle concentrations (C/C0 < 0.1). The transport profile was mathematically simulated using a one-dimensional advection-dispersion equation (ADE) and colloidal filtration theory (CFT). Additionally, interaction energy profiles based on the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory were estimated to gain a better understanding of the mechanism of f-MWCNT deposition. In light of the potential environmental consequences, the impact of real-world water systems (tap, river, lake, and ground water) on the transport behaviour of f-MWCNTs was also investigated. The study considerably advances our understanding of the various physicochemical and environmental factors that can critically impact the transport of f-MWCNT in porous media, which could prove beneficial for environmental applications and risk management.

Enhanced propagation of intracellular and extracellular antibiotic resistance genes in municipal wastewater by microplastics

Microplastics (MPs) are an emerging global concern as they are abundant in the environment and can act as vectors of various contaminants. However, whether and how MPs can be vectors of antibiotic resistance genes (ARGs), especially extracellular ARGs (eARGs), remains far from explicit. This study addresses the adsorption of both intracellular ARGs (iARGs) and eARGs by four types of MPs in municipal wastewater, and then explores the potential horizontal gene transfer of iARGs and eARGs exposed to MPs. Results indicate that though MPs significantly adsorbed both iARGs and eARGs, eARGs were adsorbed with a significantly higher fold enrichment (2.0–5.0 log versus 2.0–3.3 log) and rate (0.0056 min−1 versus 0.0037 min−1) than iARGs. While all four types of MPs adsorbed ARGs, polypropylene MPs showed the highest adsorption capacity for ARGs. Background constituents such as humic acid and antibiotics significantly inhibited adsorption of iARGs, but not eARGs on MPs. The presence of sodium chloride didn't significantly affect adsorption of iARGs or eARGs. The adsorption of ARGs was well explained by the extended Derjaguin–Landau–Verwey–Overbeek (XDLVO) interaction energy profile. Higher eARG adsorption was attributed to a lower energy barrier between MPs and eARGs than that between MPs and iARGs. Exposure to MPs enhanced horizontal gene transfer of both iARGs and eARGs by 1.5 and 2.0 times, respectively. The improved contact potential between donors and recipients, as well as the increased cell permeability of recipients induced the improved horizontal gene transfer by MPs. This study underscores the need to address ARG propagation through adsorption to MPs.

N'-(Pyridin-3-ylmethylene)benzenesulfonohydrazide: Crystal structure, DFT, Hirshfeld surface and in silico anticancer studies

A new Schiff base, N'-(pyridin-3-ylmethylene)benzenesulfonohydrazide, was synthesized and characterized by elemental analysis, IR, Mass, 1H NMR and 13C NMR spectroscopy, and single-crystal X-ray determination. The asymmetric molecule crystallized in the monoclinic crystal system and P2(1)/c space group. Crystal data for C12H11N3O2S: a = 9.7547(4) Å, b = 9.8108(4) Å, c = 13.1130(5) Å, β = 109.038(2)°, V = 1186.29(8) Å3, Z = 4, μ(MoKα) = 0.270 mm-1, Dcalc = 1.463 g/cm3, 13338 reflections measured (5.296° ≤ 2Θ ≤ 55.484°), 2790 unique (Rint = 0.0494, Rsigma = 0.0400) which were used in all calculations. The final R1 was 0.0345 (I &gt; 2σ(I)) and wR2 was 0.0914 (all data). In the crystal structure of the compound C12H11N3O2S, molecules are linked in a continuous chain by intermolecular of N∙∙∙HN=N hydrogen bonds. The pyridine moiety is planar, while the benzenesulfonohydrazide group adopts a gauche conformation about C-S-N angle (105.54°). The Hirshfeld surface analysis and fingerprint plots were used to establish the presence, nature, and percentage contribution of the different intermolecular interactions, including N-H∙∙∙N, C-H∙∙∙O, C-H∙∙∙C, and π∙∙∙π interactions, with the C-H contacts having the most significant contribution. The pairwise interaction energies were calculated at the B3LYP/6-31G(d,p) level of theory, and interaction energy profiles showed that the electrostatic forces had the most significant contribution to the total interaction energies of the different molecular pairs in the crystal. In-silico technique was used to examine the compound as a possible anticancer agent. The molecule demonstrated zero violation of the criteria of Lipinski’s rule of five with a polar surface area of 116.03 Å2. The molecule displayed favorable binding interactions with ten selected validated anticancer protein targets ranging from -9.58 to -11.95 kcal/mol and -2.73 to -5.73 kcal/mol on scoring and rescoring, respectively, with London dG and Affinity dG scoring functions. Two proteins; farnesyl transferase and signaling protein, preferred interactions with the Schiff-base over their co-crystallized inhibitors according to London dG scoring. Analysis of binding poses indicated that the Schiff-base made contact with amino acid residues of the two proteins through the N-H, sulphonyl oxygen, and phenyl groups, and this could be exploited in chemical and structural modification towards activity optimization.

Bimodal Nanocomposite Platform with Antibiofilm and Self-Powering Functionalities for Biomedical Applications.

Advances in microelectronics and nanofabrication have led to the development of various implantable biomaterials. However, biofilm-associated infection on medical devices still remains a major hurdle that substantially undermines the clinical applicability and advancement of biomaterial systems. Given their attractive piezoelectric behavior, barium titanate (BTO)-based materials have also been used in biological applications. Despite its versatility, the feasibility of BTO-embedded biomaterials as anti-infectious implantable medical devices in the human body has not been explored yet. Here, the first demonstration of clinically viable BTO-nanocomposites is presented. It demonstrates potent antibiofilm properties against Streptococcus mutans without bactericidal effect while retaining their piezoelectric and mechanical behaviors. This antiadhesive effect led to ∼10-fold reduction in colony-forming units in vitro. To elucidate the underlying mechanism for this effect, data depicting unfavorable interaction energy profiles between BTO-nanocomposites and S. mutans using the classical and extended Derjaguin, Landau, Verwey, and Overbeek theories is presented. Direct cell-to-surface binding force data using atomic force microscopy also corroborate reduced adhesion between BTO-nanocomposites and S. mutans. Interestingly, the poling process on BTO-nanocomposites resulted in asymmetrical surface charge density on each side, which may help tackle two major issues in prosthetics-bacterial contamination and tissue integration. Finally, BTO-nanocomposites exhibit superior biocompatibility toward human gingival fibroblasts and keratinocytes. Overall, BTO-embedded composites exhibit broad-scale potential to be used in biological settings as energy-harvestable antibiofilm surfaces.

Mechanism of anti-proteins adsorption behavior on superhydrophobic titanium surface

Comprehensively understanding the albumin and fibrinogen adsorption behaviors is of fundamental significance for blood-contacting devices to effectively prevent the proteins adsorption. First, a controllable superhydrophobic surface presented great repellence to different liquids with water contact angle 165.2°, plasma contact angle 154.8° and blood contact angle 152.1°. Secondly, the albumin and fibrinogen adhesion tests indicated that the pure titanium surface was fully covered by the proteins layer while only a small amount of the proteins adhered to the superhydrophobic surface. Furthermore, the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) model was built by considering the Lifshitz-van der Waals (LW), the Lewis acid-base (AB) and the electrostatic double-layer (EL) interactions, the positive value of total interaction energy profile suggested that an overall repulsive interaction between the protein molecules and superhydrophobic surface happened at a small separation distance. Finally, the hollow tubes with inner superhydrophobic surface were implanted into carotid artery of rabbits for two weeks. The content of N element measured by EDS mapping provide a new evidence that superhydrophobic surface owns a great resistance of the proteins absorption, and no thrombosis or blood cells adhered to the superhydrophobic surface. This research revealed the mechanism that superhydrophobic modification could effectively prevent the adsorption of plasma proteins, which could provide some theoretical basis to help design the blood-contacting devices with great hemocompatibility.

Colloid Interaction Energies for Surfaces with Steric Effects and Incompressible and/or Compressible Roughness

Colloid aggregation and retention in the presence of macromolecular coatings (e.g., adsorbed polymers, surfactants, proteins, biological exudates, and humic materials) have previously been correlated with electric double layer interactions or repulsive steric interactions, but the underlying causes are not fully resolved. An interaction energy model that accounts for double layer, van der Waals, Born, and steric interactions as well as nanoscale roughness and charge heterogeneity on both surfaces was extended, and theoretical calculations were conducted to address this gap in knowledge. Macromolecular coatings may produce steric interactions in the model, but non-uniform or incomplete surface coverage may also create compressible nanoscale roughness with a charge that is different from the underlying surface. Model results reveal that compressible nanoscale roughness reduces the energy barrier height and the magnitude of the primary minimum at separation distances exterior to the adsorbed organic layer. The depth of the primary minimum initially alters (e.g., increases or decreases) at separation distances smaller than the adsorbed organic coating because of a decrease in the compressible roughness height and an increase in the roughness fraction. However, further decreases in the separation distance create strong steric repulsion that dominates the interaction energy profile and limits the colloid approach distance. Consequently, adsorbed organic coatings on colloids can create shallow primary minimum interactions adjacent to organic coatings that can explain enhanced stability and limited amounts of aggregation and retention that have commonly been observed. The approach outlined in this manuscript provides an improved tool that can be used to design adsorbed organic coatings for specific colloid applications or interpret experimental observations.

Stability of nanobubbles in different salts solutions

The stability of nanobubbles in electrolyte solutions under different ion valence values was studied using deionized water, NaCl, Na2SO4, Na3PO4, CaCl2, and FeCl3. Nanobubbles were generated using hydrodynamic cavitation, and bubbles were tested for size and zeta potential. All the samples were stable for one week with no significant deviation in either bubble size or zeta potential values. The variation of size and zeta potential among six samples can be attributed to the solution properties and was mainly dependent on solution pH and the cation valency. The ion profiles revealed that the cation concentration at the bubble surface was higher than that of bulk, confirming that the bubbles were negatively charged for neutral and high pH values (≥4) under low valency cation adsorption. The high valency cations have the potential to neutralize or completely reverse the bubble charge. Anions or co-ions have minimal effect on the surface potential or the surface charge. The calculated internal pressures of bubble were unrealistically high, suggesting that the surface tension should be lower than that of water for nanobubble solutions. The interaction energy profile shows no significant energy barrier that overcomes the attractive van der Waals forces for all the solutions, except NaCl which had a 1.87 × 10−20 J barrier at a 5 nm separation distance. However, with the recorded stable bubbles, the calculation of the attractive van der Waals forces produced unrealistic values indicating that the Hamaker constant used for the calculation may not be valid at the nanobubble gas-liquid interface. This revealed that nanobubbles should contain exceptional interfacial properties that need to be carefully investigated and evaluated.

Revisiting allostery in CREB-binding protein (CBP) using residue-based interaction energy.

CREB-binding protein (CBP) is a multi-subunit scaffold protein complex in transcription regulation process, binding and interacting with ligands such as mixed-lineage leukemia (MLL) and c-Myb allosterically. Here in this study, we have revisited the concept of allostery in CBP via residue-based interaction energy calculation based on molecular dynamics (MD) simulations. To this end, we conducted MD simulations of KIX:MLL:c-Myb ternary complex, its binary components and kinase-inducible domain (KID) interacting domain (KIX) backbone. Interaction energy profiles and cross correlation analysis were performed and the results indicated that KIX:MLL and KIX:c-Myb:MLL complexes demonstrate significant similarities according to both analysis methods. Two regions in the KIX backbone were apparent from the interaction energy and cross correlation maps that hold a key to allostery phenomena observed in CBP. While one of these regions are related to the ligand binding residues, the other comprises of L12-G2 loop and α3 helix regions that have been found to have a significant role in allosteric signal propagation. All in all, residue-based interaction energy calculation method is demonstrated to be a valuable calculation technique for the detection of allosteric signal propagation and ligand interaction regions.

Quantum Mechanical Investigation of Three-Dimensional Activity Cliffs Using the Molecules-in-Molecules Fragmentation-Based Method.

The concept of activity cliff (AC) (i.e., a small structural modification resulting in a substantial bioactivity change) is widely encountered in medicinal chemistry during compound design. Whereas the study of ACs is of high interest as it provides a wealth of opportunities for effective drug design, its practical application in the actual drug development process has been difficult because of significant computational challenges. To provide some understanding of the ACs, we have carried out a rigorous quantum-mechanical investigation of the electronic interactions of a wide range of ACs (205 cliffs formed by 261 protein-ligand complexes covering 37 different receptor types) using multilayer molecules-in-molecules (MIM) fragmentation-based methodology. The MIM methodology enables performing accurate high-level quantum mechanical (QM) calculations at a substantially lower computational cost, while allowing for a quantitative decomposition of the protein-ligand binding energy into the contributions from individual residues, solvation, and entropy. Our investigation in this study is mainly focused on whether the QM binding energy calculation can correctly identify the higher potency cliff partner for a given ligand pair having a sufficiently high activity difference. We have also analyzed the effect of including crystal water molecules as a part of the receptor as well as the impact of ligand desolvation energy on the correct identification of the more potent ligand in a cliff pair. Our analysis reveals that, in the majority of the cases, the AC prediction could be significantly improved by carefully identifying the critical crystal water molecules, whereas the contribution from the ligand desolvation also remains essential. Additionally, we have exploited the residue-specific interaction energies provided by MIM to identify the key residues and interaction hot-spots that are responsible for the experimentally observed drastic activity changes. The results show that our MIM fragmentation-based protocol provides comprehensive interaction energy profiles that can be employed to understand the distinctiveness of ligand modifications, for potential applications in structure-based drug design.

Influence of graphene oxide nanoparticles on the transport and cotransport of biocolloids in saturated porous media

This study examines the effect of graphene oxide (GO) nanoparticles (NPs) on the transport (individual species) and cotransport (simultaneous transport) of three biocolloids (Escherichia (E.) coli, Enterococcus (E.) faecalis and Staphylococcus (S.) aureus) in water saturated porous media. Flowthrough experiments were performed in 30-cm long laboratory columns packed with quartz sand. All of the experiments were conducted at room temperature (22 °C), pH = 7, and ionic strength Is = 2 mM. The results from the cotransport experiments indicated that the mass recovery values for all biocolloids, calculated based on total biocolloid concentration in the effluent, were reduced in the presence of GO NPs. The strains E. coli and E. faecalis were shown to be more vulnerable to GO NPs than S. aureus. Temporal moments of the breakthrough concentrations suggested that the presence of GO NPs significantly influenced the fate and transport of the three biocolloids. Extended DLVO theory was used to quantify the various interaction energy profiles, based on electrokinetic and hydrodynamic measurements.

A computational study of the molecular basis of antibiotic resistance in a DXR mutant.

Proteins of the independent mevalonate pathway for isoprenoid biosynthesis are important targets for the development of new antibacterial compounds as this pathway is present in most pathogenic organisms such as Mycobacterium tuberculosis, DPlasmodium falciparum and Escherichia coli, but is not present in mammalian species, including humans. Deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is an important target in this pathway and the most effective DXR inhibitor to date is fosmidomycin, which is used to treat malaria and, more recently, tuberculosis. Recently, Armstrong C. M. et al. showed that a mutant of DXR, S222T, induces a loss of the fosmidomycin inhibition efficiency, even though the bacteria culture is still viable and able to produce isoprenoids. As this represents a potential fosmidomycin-resistant mutation, it is important to understand the mechanism of this apparent mutation-induced resistance to fosmidomycin. Here, we used molecular dynamics simulations and Molecular Mechanics/Poisson Boltzmann Surface Area analysis to understand the structural and energetic basis of the resistance. Our results suggest that the point mutation results in changes to the structural dynamics of an active site loop that probably protects the active site and facilitates enzymatic reaction. From the simulation analysis, we also showed that the mutation results in changes in the interaction energy profiles in a way that can explain the observed activity of the mutant protein toward the natural inhibitor deoxy-D-xylulose 5-phosphate. These results should be taken into consideration in future efforts to develop new therapeutic antibiotic compounds that target DXR.

Molecular and Supramolecular Interactions in Systems with Nitroxide-Based Radicals.

Nitroxide-based radicals, having the advantage of firm chemical stability, are usable as probes in the detection of nanoscale details in the chemical environment of various multi-component systems, based on subtle variations in their electron paramagnetic resonance spectra. We propose a systematic walk through the vast area of problems and inquires that are implied by the rationalization of solvent effects on the spectral parameters, by first-principle methods of structural chemistry. Our approach consists of using state-of-the-art procedures, like Density Functional Theory (DFT), on properly designed systems, kept at the border of idealization and chemical realism. Thus, we investigate the case of real solvent molecules intervening in different configurations between two radical molecules, in comparison with radicals taken in vacuum or having the solvent that is treated by surrogate models, such as polarization continuum approximation. In this work, we selected the dichloromethane as solvent and the prototype radicals abbreviated TEMPO ((2,2,6,6-Tetramethylpiperidin-1-yl) oxyl). In another branch of the work, we check the interaction of radicals with large toroidal molecules, β-cyclodextrin, and cucurbit[6]uril, modeling the interaction energy profile at encapsulation. The drawn synoptic view offers valuable rationales for understanding spectroscopy and energetics of nitroxide radicals in various environments, which are specific to soft chemistry.