Bridge Formation Research Articles

Confined behavior of nanodroplets under electric field: A molecular dynamics simulation study

The wetting effect and related applications of nanodroplets have attracted extensive research interest. In this work, we report molecular dynamics simulations of the confinement dynamics of nanodroplets at different droplet-surface interactions, surface separations, and ion concentrations under the electric field. The results show that in the case of a single droplet, there is a critical value of surface wettability for the shape transition of the confined droplet. Below this value, the droplet shrinks into a spherical shape and attaches to the surface. Above this value, the droplet splits into two smaller droplets which locate at the bottom and top surfaces, respectively. For the two-droplet cases, a liquid bridge forms and some ions migrate into the pure water droplet under the electric field. The results reveal that the ion concentration has a significant effect on the shape evolution of droplets. The stable morphology of droplets under the electric field depends on the droplet-surface interactions as well as the ion concentration. We explore the underlying mechanisms causing the morphological transition by analyzing the intermolecular interactions and interfacial characteristics.

Design of motifs interfacial interactions by co‐evolved analysis of D‐amino acid dehydrogenase for stability enhancement

AbstractTo design D‐amino acid dehydrogenase (DAADH) for enhanced stability, the interactions of the subunit interfaces of DAADH were analyzed. Interaction network analysis of DAADH indicated that there are only weak interactions between the A and B subunits. Several co‐evolved residue pairs were selected for mutation to enhance interfacial interactions of subunits, and 11 designed DAADHs were obtained. DA06 and DA11 were selected for experimental verification for their salt bridges are 1.4 and 1.2‐fold of that of DAwild, respectively. DA11 can maintain 93% activity in 80°C, while it was only 40% for DAwild. Thermostability study indicated the half‐life of DA11 was 2‐fold of DAwild. Molecular dynamics simulations revealed that the extraordinary stability of the DA11 was due to the formation of extra interfacial salt bridges. The article provides a strategy of mutations outside the active site of enzyme by co‐evolutionary analysis which can reduce the effect of the activity‐thermostability trade‐off.

Ultra-fast Proton Conduction and Photocatalytic Water Splitting in a Pillared Metal-Organic Framework.

Proton-exchange membrane fuel cells enable the portable utilization of hydrogen (H2) as an energy resource. Current electrolytic materials have limitation, and there is an urgent need to develop new materials showing especially high proton conductivity. Here, we report the ultra-fast proton conduction in a novel metal-organic framework, MFM-808, which adopts an unprecedented topology and a unique structure consisting of two-dimensional layers of {Zr6}-clusters. By replacing the bridging formate with sulfate ligands within {Zr6}-layers, the modified MFM-808-SO4 exhibits an exceptional proton conductivity of 0.21 S·cm-1 at 85 °C and 99% relative humidity. Modeling by molecular dynamics confirms that proton transfer is promoted by an efficient two-dimensional conducting network assembled by sulfate-{Zr6}-layers. MFM-808-SO4 also possesses excellent photocatalytic activity for water splitting to produce H2, paving a new pathway to achieve a renewable hydrogen-energy cycle.

Lacustrine islands in the cultural and natural landscape of Western Slavs in the early Middle Ages

Recent research on central West Slavic sites in the Polish Lowlands (Poland) dated to the Early Middle Ages conducted within the framework of the Man in the Borderland project (NP DH) has shown that settlements located on small lake islands (Pomerania, Lubusz land) were of particular importance, alongside settlements performing complex social and political functions. Their physiognomy relates in many cases to British crannogs, as they have an anthropogenic (artificial) structure and their characteristic feature is the presence of wooden relics of structures in the form of embankments, piers and bridges. The occurrence of artifacts characteristic of social elites (militaria, merchant's accessories, jewellery) further indicates the importance of many of these sites. As a rule, they were located on the borders of former tribal territories and on the periphery of the early Piast state (8th/9th–11th century).

Osteophyte Bridge Formation Correlates with Vascular Calcification and Cardiovascular Disease in Diffuse Idiopathic Skeletal Hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy characterized by ectopic calcification of spinal cord tissue. Its etiology is possibly polygenic. However, its pathogenesis and systemic effects remain unclear. Recent studies have reported a high prevalence of DISH in heart failure patients. The authors investigated how the incidence and severity of DISH are associated with vascular calcification and the occurrence of cardiovascular events. In this retrospective chart review study, 500 patients with cardiovascular disease who underwent surgery (cardiovascular events group) and 500 patients with non-cardiovascular disease who underwent computed tomography scans (non-cardiovascular events group) were randomly selected to investigate the degree of ossification of the anterior longitudinal ligament and the incidence of DISH. We found that the incidence of DISH was higher in patients with cardiovascular events and that patients with DISH had more calcification of the coronary arteries and aorta. Next, we examined the relationship between the degree of coronary and aortic calcification, the incidence of DISH, and the degree of ossification of the anterior longitudinal ligament in the non-cardiovascular event group. The prevalence of DISH in the cardiovascular and non-cardiovascular groups was 31.4% and 16.5%, respectively (p = 0.007). Aortic calcification and a predominant degree of vascular calcification with a certain level of ossification of the anterior longitudinal ligament suggest some correlation between DISH and cardiovascular events. This study is important in understanding the pathophysiology and pathogenesis of DISH.

In the Alphaproteobacterium Hyphomicrobium denitrificans SoxR Serves a Sulfane Sulfur-Responsive Repressor of Sulfur Oxidation.

In organisms that use reduced sulfur compounds as alternative or additional electron donors to organic compounds, transcriptional regulation of genes for enzymes involved in sulfur oxidation is needed to adjust metabolic flux to environmental conditions. However, little is known about the sensing and response to inorganic sulfur compounds such as thiosulfate in sulfur-oxidizing bacteria. In the Alphaproteobacterium Hyphomicrobium denitrificans, one strategy is the use of the ArsR-SmtB-type transcriptional regulator SoxR. We show that this homodimeric repressor senses sulfane sulfur and that it is crucial for the expression not only of sox genes encoding the components of a truncated periplasmic thiosulfate-oxidizing enzyme system but also of several other sets of genes for enzymes of sulfur oxidation. DNA binding and transcriptional regulatory activity of SoxR are controlled by polysulfide-dependent cysteine modification. The repressor uses the formation of a sulfur bridge between two conserved cysteines as a trigger to bind and release DNA and can also form a vicinal disulfide bond to orchestrate a response to oxidizing conditions. The importance of the sulfur bridge forming cysteines was confirmed by site-directed mutagenesis, mass spectrometry, and gel shift assays. In vivo, SoxR interacts directly or indirectly with a second closely related repressor, sHdrR.

CYTOGENETIC EFFECTS OF SURFACTANTS

Introduction. The widespread use of surfactants in economic activity and life has led to global pollution. The negative impact of surfactants on various characteristics of living organisms has been revealed, which makes a research on the safety of surfactants extremely relevant. Aim. The aim of this work was to study the genotoxic potential of anionic and cationic surfactants. Methods. The influence of anionic (sodium stearate and alkylbenzenesulpho-acid) and cationic (Praepagen TQ) surfactants on the value of the mitotic index, as well as on the regularity of mitosis and meiosis of Triticum aestivum L. cv. Odesa fantasy by standard cytogenetic methods. Main results. Under the action of surfactants in the root meristem of sprouts, the mitotic index significantly decreased and the number of cells containing chromosomal aberrations increased. Among the abnormalities at the ana-telophase stage, cells with lagging chromosomes, fragments, the formation of chromosomal bridges, and complex disorders were observed. These changes were directly proportional to the concentration of the drugs. The action of the cationic drug was less harmful than the action of both anionic drugs. Treatment of plants with surfactants led to a highly reliable increase in the proportion of abnormal MCPs in both the first and second division of meiosis, directly proportional to the concentration of surfactants applied. No differences were found between the first and second meiotic divisions in terms of the frequency of formation of defective MCPs. Both anionic surfactants had a stronger effect than the cationic one; with the use of alkylbenzenesulfonic acid, the degree of violations in microsporocytes was the greatest. Conclusions. A significant decrease in the mitotic index and an increase in the proportion of cells containing chromosomal aberrations in the root meristem of sprouts, as well as a significant increase in the proportion of abnormal MCPs in both the first and second division of meiosis, were found to be directly proportional to the concentration of surfactant. According to all the parameters studied, the action of the cationic drug “Praepagen TQ” was milder than the action of both anionic surfactants.

Observation of Capillary Condensation and Pattern Bending Phenomena in Si Nanopillars Using <i>In Situ</i> TEM

Capillary condensation, a ubiquitous phenomenon involving the heterogeneous nucleation of liquid droplets, has significant implications in various industrial, biological, and atmospheric processes. Strong capillary forces induced by highly curved menisci of condensates can have potentially significant impact on the structural integrity and functionality of nanodevices. While the influence of surface properties on the nucleation and growth of water droplets has been extensively studied at microscale, our understanding of water condensation at the nanoscale remains limited due to experimental challenges in imaging liquids at nanometer scales. In this study, we employ in situ liquid phase TEM imaging and for the first time present real-time observations of water condensation dynamics on arrays of vertical silicon (Si) nanopillars. Experimental and simulation results show that nucleation of water droplets occurs at the edges of the nanopillars and substrate, followed by the growth of an interfacial layer resembling a corona around the nanopillars. Subsequently, the formation of bridges between adjacent growing coronas leads to the development of symmetric and asymmetric bridged nanopillar geometries. Importantly, we find that the formation of bridges can induce bending and collapse of the nanopillars, depending on their aspect ratios. Overall, this study provides valuable insights into the nanoscale dynamics of capillary condensation and paves the way for advanced engineering applications and optimization of various technological processes.

Electrically actuated characteristics and electrochemical mechanism of a flexible biomimetic artificial muscle regulated by the responsive polymer of the calcium alginate gelation

In comparison to conventional actuated techniques, the utilization of a Flexible Biomimetic Artificial Muscle (FBAM) incorporating calcium alginate hydrogel, a type of responsive polymer, offers numerous benefits including reduced weight, lower actuated voltage requirements, enhanced specific energy density, and minimal acoustic disturbances, among others. This paper presents the fabrication of the FBAM through calcium alginate gelation utilizing six calcium salts with identical Ca2+ molar mass. Subsequently, the electrically actuated characteristics and electrochemical mechanism of the FBAM were investigated, employing four evaluation indexes: peak force density (D, mN/g), operating life (Tt, s), response speed (Vr, mN/g·s), and rise time (Ts, s). The findings of this study hold significant implications for the advancement of novel responsive polymers for artificial muscles. The findings of the study indicate that the electrically actuated characteristics of FBAM were most optimal when calcium alginate gelation with CaH8I2O4 was employed. This was evidenced by the D value of 22.807 mN/g, Tt value of 1066 s, Vr value of 98 s, and Ts value of 0.1046 mN/g·s. The sufficient degree of calcium alginate gelation between sodium alginate molecule and Ca2+ cations resulted in the formation of intermolecular bridges within the calcium alginate hydrogel, which consisted of polymer β-D-mannuronic and α-L-guluronic. Notably, this gelation process was found to be inversely related to the pH level in the aqueous solution of the electrically actuated membrane.

A26 Linzer Autobahn – Herausforderungen im Rückblick und Ausblick

AbstractAfter a long planning and approval phase, the main construction work on the A26 Linz motorway began at the beginning of 2019. The new A26 road section, large parts of which are underground, will not only significantly relieve the existing inner‐city traffic routes around Linz, but will also provide an additional Danube crossing in the form of a suspension bridge with a span of over 300 m. The main elements of the first Phase of construction are the Danube Bridge and two underground branches, north and south of the Danube, with excavated cross‐sections of up to 400 m2 and ramp tunnels with tight curves.The planning of an inner‐city construction project requires the comprehensive and careful consideration of the protection of the local residents with regard to the effects of noise and vibration. It also needs the impact of the construction work on the existing traffic routes to be reduced as much as possible. The material excavated from the Freinberg tunnel and the Danube South junction must be transported away via the Danube waterway. The project‐specific framework conditions, such as the very high number of tunnel portals, the sound reflections within the Danube valley and the low overburden require considerable measures to reduce their impact during the construction phase.

Partition complex structure can arise from sliding and bridging of ParB dimers

In many bacteria, chromosome segregation requires the association of ParB to the parS-containing centromeric region to form the partition complex. However, the structure and formation of this complex have been unclear. Recently, studies have revealed that CTP binding enables ParB dimers to slide along DNA and condense the centromeric region through the formation of DNA bridges. Using semi-flexible polymer simulations, we demonstrate that these properties can explain partition complex formation. Transient ParB bridges organize DNA into globular states or hairpins and helical structures, depending on bridge lifetime, while separate simulations show that ParB sliding reproduces the multi-peaked binding profile observed in Caulobacter crescentus. Combining sliding and bridging into a unified model, we find that short-lived ParB bridges do not impede sliding and can reproduce both the binding profile and condensation of the nucleoprotein complex. Overall, our model elucidates the mechanism of partition complex formation and predicts its fine structure.

Synthesis of Pseudooligosaccharides Related to the Capsular Phosphoglycan of Haemophilus influenzae Type a.

Synthesis of spacer-armed pseudodi-, pseudotetra-, and pseudohexasaccharides related to the capsular phosphoglycan of Haemophilus influenzae type a, the second most virulent serotype of H. influenzae (after type b), was performed for the first time via iterative chain elongation using H-phosphonate chemistry for the formation of inter-unit phosphodiester bridges. These compounds were prepared for the design of neoglycoconjugates, as exemplified by the transformation of the obtained pseudohexasaccharide derivative into a biotinylated glycoconjugate suitable for use in immunological studies, particularly in diagnostic screening systems as a coating antigen for streptavidin-coated plates and chip slides.

Fusion rate of Escherichia coli-derived recombinant human bone morphogenetic protein-2 compared with local bone autograft in posterior lumbar interbody fusion for degenerative lumbar disorders

BACKGROUND CONTEXTThe use of recombinant human bone morphogenetic proteins-2 (rhBMP-2) for spinal fusion has been reported to be effective. However, most studies have focused on posterolateral and anterior lumbar interbody fusion, and few have investigated posterior lumbar interbody fusion (PLIF). PURPOSEThis study aimed to determine the effectiveness and safety of the delivery of Escherichia coli-derived rhBMP-2 (E.BMP-2) with hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) poloxamer hydrogel composite carriers for PLIF. STUDY DESIGNA retrospective study. PATIENT SAMPLEPatients who underwent 1 to 3 levels of PLIF for lumbar degenerative disc disorders between 2015 and 2020 with a follow-up of ≥1 year were enrolled. In total, 254 patients (357 levels) were included in the analysis. The evaluation was performed at each segment level. In the E.BMP-2 group, 160 patients (221 levels) received autologous local bone with E.BMP-2 (maximum 0.5 mg/level), and in the control group, 94 patients (136 levels) received only local bone graft. OUTCOME MEASURESThe primary outcome of this study was to compare the X-ray and CT fusion rates between the two groups. Secondary outcomes included analysis of the patients’ clinical outcomes and postoperative complications on CT scans. METHODSClinical evaluations were performed using a visual analog scale for back pain, the Oswestry Disability Index for disability, and physical and mental component summaries of the Short Form 36-Item Form Health Survey to assess functional effects and quality of life. The fusion was evaluated using radiography and CT. On radiography, solid fusion was defined when the difference between extension and flexion was less than 5°. On CT, solid fusion was defined when the upper and lower vertebral bodies were connected by the trabecular bone (bone bridge formation). In addition, complications such as osteolysis, cage subsidence, and screw loosening were investigated using CT. RESULTSAll clinical results for low back pain, disability, and quality of life in both groups were excellent and showed statistically significant improvements compared with baseline (p<.0001). According to the X-ray evaluations, fusion was achieved in 92.31% (204/221) of the patients in the E.BMP-2 group and 82.35% (112/136) of the patients in the control group (p=.0041). According to the CT evaluations, the fusion rates were 93.21% (206/221) and 88.24% (120/136) in the E.BMP-2 and control groups (p=.1048), respectively. Except for screw loosening, which had a significantly higher incidence in the control group (p=.0014), the rates of most postoperative complications were not significantly different between the groups. CONCLUSIONSThis study demonstrated that the adjunctive use of a low dose of E.BMP-2 with HA and β-TCP hydrogel can effectively promote bone fusion, making it a promising option for patients with limited autograft availability or compromised bone quality in PLIF.

DEM-LBM coupling for partially saturated granular assemblies

In this paper, we propose a phase-field-based Lattice Boltzmann Method (LBM) model coupled with the Discrete Element Method (DEM) for simulating unsaturated granular media over a large range of degrees of saturation. The formation of capillary bridges between grains is computed via an LBM scheme that solves Navier–Stokes and Allen–Cahn equations for multi-phase flow in complex geometries. As for the motions of the grains, these are computed within DEM where the contact behavior between spherical particles is based on a simple elastic–plastic contact law. Using an efficient DEM-LBM coupling framework, capillarity effects are explored at the pore scale with the collapse of a sandcastle as a classic illustration. This is done by considering an assembly of several thousands of spherical particles connected by capillary bridges for different degrees of saturation. It is shown that the mean capillary stress increases with the degree of saturation up to a certain threshold beyond which capillary stress drops until complete saturation. In addition, the Soil Water Characteristic Curve is qualitatively recovered and compared to a theoretical model. As such, the proposed DEM-LBM coupling scheme becomes a viable numerical tool that can explicitly model and explore pore-scale phenomena in unsaturated soils.

Micro-adhesive structure inspired by tree frog toe pads fabricated by femtosecond laser processing of PVA sponge

Tree frogs of the species Zhangixalus arboreus are known to generate high adhesive force in wet environments due to the microstructure of their toe pads. Inspired by this toe pads, we fabricated a micro-adhesive structure with hexagonal channels (500, 375, 250, 188, and 125 μm per side) on the surface of a polyvinyl alcohol sponge. Femtosecond laser processing was used to create fine grooves on the surface of the sponge. When the sponge is pressed against the object, the liquid in the sponge is released onto the contact surface. In wet conditions, it is important to maintain the proper thickness of the liquid phase between the microstructure and the object, and this is achieved by the sponge. The characteristics of friction (shear force) between soft and hard objects differ from those between hard materials. When the liquid present on the contact surface is very small, the surface tension of the liquid phase causes the formation of numerous microcapillary bridges, which generate shear forces. The shear force was evaluated by soaking the sponge with water, pressing (300, 400, 500 μm) a flat or uneven surface against the sponge, and then sliding (20, 40 mm/s) the object. The maximum shear force was 0.22 N for the flat surface and 0.34 N for the uneven surface. It was found that the shear force became smaller when the structure became too fine. This phenomenon is due to the agglomeration of the microstructures.

Oxygen Bridge Formed by Doping Nonmetal Atoms into Cationic Vacancies To Enhance the Photoelectrochemical Oxygen Evolution Reaction.

To enhance photoelectrochemical (PEC) water splitting for renewable energy conversion, the conventional strategy is doping nonmetals into anionic vacancies. Compared to anionic vacancies, cationic vacancies are theoretically more effective and reliable for anchoring nonmetals owing to their larger radii and unique advantages. The current research mainly focuses on anionic vacancies, while there are few studies on cationic vacancies due to high formation energy and challenging characterizations by convenient techniques. To overcome the current limitations, nonmetallic S and P atoms are successfully doped into cationic vacancies on the TiO2 surface for tuning local electronic structures. In contrast to the traditional strategy of reducing the bandgaps, nonmetallic atom doping into cationic vacancies facilitates efficient electronic regulation for PEC enhancement without changing the bandgap. The enhanced performance is attributed to the formation of an oxygen bridge, which can accumulate electrons from surrounding S/P atoms. Significantly, the electron-enriched oxygen bridge efficiently transfers electrons to activate reaction site Ti, which can promote the oxygen evolution reaction performance. Density functional theory calculations reveal that the decrease of reaction energy barriers and the optimization of local electron distribution are conducive to electronic transmission. This would provide a high-efficiency electronic tuning strategy for improving PEC performance.

Clinical evaluation of the perception of post-trauma paresthesia in the mandible, using a biomimetic material: A preliminary study in humans

There is a great effort from numerous research groups in the development of materials and therapeutic strategies for the functional recovery of patients who have suffered peripheral nerve injuries (PNI). In an article in vivo, the formation of a nerve bridge was observed, reconnecting the distal and proximal stumps, in the sciatic nerve of rats, indicating the effective participation of the biomaterial in the recovery of peripheral nerve injuries. For the current pilot study, 15 cases of multiple fractures of the mandible, with involvement of the inferior alveolar nerve (IAN) were selected and studied: JC (control cases) n = 6 with conventional treatment, and JT (treated cases) n = 9, with the use of biomimetic biomaterial. The evaluation of the return to sensitivity was measured through a self-assessment, where the patients assigned scores from 0 to 10, where zero (0) represented the complete absence of sensitivity and ten (10) the normality of the perception of local sensitivity. Patients were evaluated from the preoperative period to the 360th day. The statistical results obtained by the t-Student, Shapiro-Wilk normality and non-parametric One-Way ANOVA tests indicated statistically significant differences (p < 0.005; 0.005 e 0.5 respectively), between the two treatments, which were reflected in the clinical results observed, we also calculate the size of the effect represented by ϵ2, calculated by Cohen's d. The results indicate a great difference between the treatments performed,ϵ2 = 1.00. In the 6 cases followed up in the JC group, four remained with a significant deficit until the end of the evaluations and two indicated the remission of the lack of sensitivity in this period. In the JT group, in 28 days, all cases indicated complete remission of the lack of sensitivity with healing concentration. In one of the cases where there was a complete rupture of the mental nerve, the (score-10) was observed in 60 days. The observed results indicate the existence of a statistical significance between the groups and an important relationship when using the biomimetic biomaterial during the recovery of the perception of sensitivity in polytraumatized patients, compatible with the results observed in laboratory animals, which may indicate its clinical feasibility in the reduction of sequelae in PNI.

Identification of a Salt Bridge That Is Functionally Important for Chemokine Receptor CXCR1 but not CXCR2.

CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have high sequence similarity and overlapping chemokine ligand profiles. Residue positions 3.32 and 7.39 are critical for signal transduction in the related CXCR4, and in these positions CXCR1 and CXCR2 contain oppositely charged residues (Lys3.32 and Glu7.39). Experimental and computed receptor structures reveal the possible formation of a salt bridge between transmembrane (TM) helices 3 and 7 via these two residues. To investigate the functional importance of Lys1173.32 and Glu2917.39 in CXCR1, along with the flanking Glu1183.33, we performed a signaling study on 16 CXCR1 mutants using two different CXCL8 isoforms. While single Ala-mutation (K1173.32A, E2917.39A) and charge reversal (K1173.32E, E2917.39K) resulted in nonfunctional receptors, double (K1173.32E-E2917.39K) and triple (K1173.32E-E1183.33A-E2917.39K) mutants rescued CXCR1 function. In contrast, the corresponding mutations did not affect the CXCR2 function to the same extent. Our findings show that the Lys3.32-Glu7.39 salt bridge between TM3 and -7 is functionally important for CXCR1 but not for CXCR2, meaning that signal transduction for these highly homologous receptors is not conserved.

Precursor of disintegration of Greenland's largest floating ice tongue

Abstract. The largest floating tongue of Greenland’s ice sheet, Nioghalvfjerdsbræ, has been relatively stable with respect to areal retreat until 2022. Draining more than 6 % of the ice sheet, a disintegration of Nioghalvfjerdsbræ's floating tongue and subsequent acceleration due to loss in buttressing are likely to lead to sea level rise. Therefore, the stability of the floating tongue is a focus of this study. We employed a suite of observational methods to detect recent changes at the calving front. We found that the calving style has changed since 2016 at the southern part of the eastern calving front, from tongue-type calving to a crack evolution initiated at frontal ice rises reaching 5–7 km and progressing further upstream compared to 2010. The calving front area is further weakened by an area upstream of the main calving front that consists of open water and an ice mélange that has substantially expanded, leading to the formation of a narrow ice bridge. These geometric and mechanical changes may be a precursor of instability of the floating tongue. We complement our study by numerical ice flow simulations to estimate the impact of future ice-front retreat and complete ice shelf disintegration on the discharge of grounded ice. These idealized scenarios reveal that a loss of the south-eastern area of the ice shelf would lead to a 0.2 % increase in ice discharge at the grounding line, while a sudden collapse of the frontal area (46 % of the floating tongue area) will enhance the ice discharge by 5.1 % due to loss in buttressing. Eventually, a full collapse of the floating tongue increases the grounding line flux by 166 %.

Hydration and Structural Adaptations of the Human CYP1A1, CYP1A2, and CYP1B1 Active Sites by Molecular Dynamics Simulations.

Cytochromes CYP1A1, CYP1A2, and CYP1B1, the members of the cytochrome P450 family 1, catalyze the metabolism of endogenous compounds, drugs, and non-drug xenobiotics which include substances involved in the process of carcinogenesis, cancer chemoprevention, and therapy. In the present study, the interactions of three selected polymethoxy-trans-stilbenes, analogs of a bioactive polyphenol trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) with the binding sites of CYP1 isozymes were investigated with molecular dynamics (MD) simulations. The most pronounced structural changes in the CYP1 binding sites were observed in two substrate recognition sites (SRS): SRS2 (helix F) and SRS3 (helix G). MD simulations show that the number and position of water molecules occurring in CYP1 APO and in the structures complexed with ligands are diverse. The presence of water in binding sites results in the formation of water-protein, water-ligand, and bridging ligand-water-protein hydrogen bonds. Analysis of the solvent and substrate channels opening during the MD simulation showed significant differences between cytochromes in relation to the solvent channel and the substrate channels 2c, 2ac, and 2f. The results of this investigation lead to a deeper understanding of the molecular processes that occur in the CYP1 binding sites and may be useful for further molecular studies of CYP1 functions.