Radiation-Induced De Novo Defects in Metal-Organic Frameworks Boost CO2 Sorption.

Defects in metal-organic frameworks (MOFs) can significantly change their local microstructures, thus notably leading to an alteration-induced performance in sorption or catalysis. However, achieving de novo defect engineering in MOFs under ambient conditions without the scarification of their crystallinity remains a challenge. Herein, we successfully synthesize defective ZIF-7 through 60Co gamma ray radiation under ambient conditions. The obtained ZIF-7 is defect-rich but also has excellent crystallinity, enhanced BET surface area, and hierarchical pore structure. Moreover, the amount and structure of these defects within ZIF-7 were determined from the two-dimensional (2D) 13C-1H frequency-switched Lee-Goldburg heteronuclear correlation (FSLG-HETCOR) spectra, continuous rotation electron diffraction (cRED), and high-resolution transmission electron microscopy (HRTEM). Interestingly, the defects in ZIF-7 all strongly bind to CO2, leading to a remarkable enhancement of the CO2 sorption capability compared with that synthesized by the solvothermal method.

Cytocompatibility of Ti3C2Tx MXene with Red Blood Cells and Human Umbilical Vein Endothelial Cells and the Underlying Mechanisms.

Two-dimensional (2D) nanomaterials have been widely used in biomedical applications because of their biocompatibility. Considering the high risk of exposure of the circulatory system to Ti3C2Tx, we studied the cytocompatibility of Ti3C2Tx MXene with red blood cells (RBCs) and human umbilical vein endothelial cells (HUVECs) and showed that Ti3C2Tx had excellent compatibility with the two cell lines. Ti3C2Tx at a concentration as high as 200 µg/mL caused a negligible percent hemolysis of 0.8%. By contrast, at the same treatment concentration, graphene oxide (GO) caused a high percent hemolysis of 50.8%. Scanning electron microscopy revealed that RBC structures remained intact in the Ti3C2Tx treatment group, whereas those in the GO group completely deformed, sunk, and shrunk, which resulted in the release of cell contents. This difference can be largely ascribed to the distinct surficial properties of the two nanosheets. In specific, the fully covered surface-terminating -O and -OH groups leading to Ti3C2Tx had a very hydrophilic surface, thereby hindering its penetration into the highly hydrophobic interior of the cell membrane. However, the strong direct van der Waals attractions coordinated with hydrophobic interactions between the unoxidized regions of GO and the lipid hydrophobic tails can still damage the integrity of the cell membranes. In addition, the sharp and keen-edged corners of GO may also facilitate its relatively strong cell membrane damage effects than Ti3C2Tx. Thus, the excellent cell membrane compatibility of Ti3C2Tx nanosheets and their ultraweak capacity to provoke excessive ROS generation endowed them with much better compatibility with HUVECs than GO nanosheets. These results indicate that Ti3C2Tx has much better cytocompatibility than GO and provide a valuable reference for the future biomedical applications of Ti3C2Tx.

Metal-Organic Framework Membrane Constructor: A Tool for High-Throughput Construction of Metal-Organic Framework Membrane Models.

With the rapid development of metal-organic framework (MOF) membranes for separation applications, computational screening of their separation performance has attracted increasing interest in the design and fabrication of such materials. Although bulk crystal models in MOF databases are often used to represent MOF membrane structures, membrane models in slab geometries are still essential for researchers to simulate the separation performance, particularly to understand the effects of the surface/interface structure, pore sieving, and exposed lattice plane on guest permeability. However, to date, no database or method has been established to provide researchers with numerous membrane models, restricting the further development of related theoretical studies. Herein, we propose an algorithm and develop a tool called the "MOF-membrane constructor" to realize the high-throughput construction of membrane models based on the MOF crystal structures. Using this tool, membrane models can be generated with desired sizes, reasonable surface terminations, and assigned exposed crystal planes. The tool can also deduce the most prominent surface in the Bravais-Friedel-Donnay-Harker morphology or identify the pores in MOF crystals and automatically determine an exposed plane for each membrane model. Thus, an MOF-membrane database can be established rapidly according to user simulation requirements. This study can considerably improve the efficiency of building MOF membrane models and may be beneficial for the future development of simulation studies on MOF membranes.

d-Band Center of Rare Earth Oxides Determines Biotransformation-Induced Cell Membrane Damage.

Biotransformation of rare earth oxide (REO) nanoparticles on biological membranes may trigger a series of adverse health effects in biosystems. However, the physicochemical mechanism of the complicated biotransformation behavior remains elusive. By investigating the distinctly different biotransformation behavior of two typical REOs (Gd2O3 and CeO2) on erythrocyte membranes, we demonstrate that dephosphorylation by stripping phosphate from phospholipids correlates highly with the membrane destructive effects of REOs. Density functional theory calculations decode the decisive role of the d-band center in dephosphorylation. Furthermore, using the d-band center as an electronic descriptor, we unravel a universal structure-activity relationship of the membrane-damaging capability of 13 REOs (R2 = 0.82). The effect of ion release on dephosphorylation and physical damage to cell membranes by Gd2O3 are largely excluded. Our findings depict a clear physicochemical microscopic picture of the biotransformation of REOs on the nano-bio interface, providing a theoretical basis for safe application of REOs.

Highly Selective Electrocatalytic Oxidation of Amines to Nitriles Assisted by Water Oxidation on Metal-Doped α-Ni(OH)2.

Selective oxidation to synthesize nitriles is critical for feedstock manufacturing in the chemical industry. Current strategies typically involve substitutions of alkyl halides with toxic cyanides or the use of strong oxidation reagents (oxygen or peroxide) under ammoxidation/oxidation conditions, setting considerable challenges in energy efficiency, sustainability, and production safety. Herein, we demonstrate a facile, green, and safe electrocatalytic route for selective oxidation of amines to nitriles under ambient conditions, assisted by the anodic water oxidation on metal-doped α-Ni(OH)2 (a typical oxygen evolution reaction catalyst). By controlling the balance between co-adsorption of the amine molecule and hydroxyls on the catalyst surface, we demonstrate that Mn doping significantly promotes the subsequent chemical oxidation of amines, resulting in Faradaic efficiencies of 96% for nitriles under ≥99% conversion. This anodic oxidation is further coupled with cathodic hydrogen evolution for overall atomic economy and additional green energy production.

Thermodynamics-Kinetics-Balanced Metal-Organic Framework for In-Depth Radon Removal under Ambient Conditions.

Radon (Rn), a ubiquitous radioactive noble gas, is the main source of natural radiation to human and one of the major culprits for lung cancer. Reducing ambient Rn concentration by porous materials is considered as the most feasible and energy-saving option to lower this risk, but the in-depth Rn removal under ambient conditions remains an unresolved challenge, mainly due to the weak van der Waals (vdW) interaction between inert Rn and adsorbents and the extremely low partial pressure (<1.8 × 10-14 bar, <106 Bq/m3) of Rn in air. Adsorbents having either favorable adsorption thermodynamics or feasible diffusion kinetics perform poorly in in-depth Rn removal. Herein, we report the discovery of a metal-organic framework (ZIF-7-Im) for efficient Rn capture guided by computational screening and modeling. The size-matched pores in ZIF-7-Im abide by the thermodynamically favorable principle and the exquisitely engineered quasi-open apertures allow for feasible kinetics with little sacrifice of sorption thermodynamics. The as-prepared material can reduce the Rn concentration from hazardous levels to that below the detection limit of the Rn detector under ambient conditions, with an improvement of at least two orders of amplitude on the removal depth compared to the currently best-performing and only commercialized material activated charcoal.

In(III) Metal-Organic Framework Incorporated with Enzyme-Mimicking Nickel Bis(dithiolene) Ligand for Highly Selective CO2 Electroreduction.

Inspired by the exciting physical/chemical properties in metal-organic frameworks (MOFs) of the redox-active tetrathiafulvalene (TTF) ligands, nickel bis(dithiolene-dibenzoic acid), [Ni(C2S2(C6H4COOH)2)2], has been designed and developed as an inorganic analogue of the corresponding TTF-type donors (such as tetrathiafulvalene-tetrabenzoate, TTFTB), where a metal site (Ni) replaces the central C═C bond. In this work, [Ni(C2S2(C6H4COOH)2)2] and In3+ have been successfully assembled into a three-dimensional MOF, (Me2NH2+){InIII-[Ni(C2S2(C6H4COO)2)2]}·3DMF·1.5H2O (1, DMF = N,N-dimethylformamide), with satisfying chemical and thermal stabilities. With the combination of reversible redox activity and unsaturated metal sites originated from [Ni(C2S2(C6H4COOH)2)2], 1 showed a significantly enhanced performance in electrocatalytic CO2 reduction compared with the isomorphic MOF, (Me2NH2+)[InIII-(TTFTB)]·0.7C2H5OH·DMF (2, with TTFTB ligand). More importantly, by mimicking the active [NiS4] sites of formate dehydrogenase and CO-dehydrogenase, a prominently higher conversion rate and Faradaic efficiency (FE), with FEHCOO- increasing from 54.7% to 89.6% (at -1.3 V vs RHE, jHCOO- = 36.0 mA cm-2), were achieved in 1. Mechanistic investigations further confirm that [NiS4] can serve as a CO2 binding site and efficient catalytic center. This unprecedented effect of redox-active nickel dithiolene-based MOF catalysts on the performance of electroreduction of CO2 provides an important strategy for designing stable and efficient crystalline enzyme-mimicking catalysts for the conversion of CO2 into high-value chemical stocks.

Lanosterol reduces the aggregation propensity of ultraviolet-damaged human γD-crystallins: a molecular dynamics study.

Ultraviolet (UV) radiation-induced oxidation of tryptophan (Trp) to kynurenine (KN) (TRP > KN) in human γD-crystallins (HγD-Crys) promotes the conversion of proteins into partially unfolded species that act as important precursors for sequential large-scale aggregation. Herein, we report that lanosterol shows protective activity to the structure of the TRP > KN mutant HγD-Crys, particularly its N-terminal domain (N-td), by using all-atom molecular dynamics simulations. The Trp68 > KN mutation significantly destabilizes the originally highly stable "Tyr55-Trp68-Tyr62" cluster, thereby causing loop2, where the mutation occurs, to become very flexible. The large fluctuation of loop2 induces cracks, which appear on the protein surface, resulting in the intrusion of water molecules into the hydrophobic core of the N-td. This event eventually triggers the unfolding of the N-td. However, lanosterol can suppress the large fluctuation of loop2 to protect the structural stability of the mutant N-td, thus reducing the aggregation propensity of the TRP > KN mutant HγD-Crys. This structure protective activity of lanosterol arises from its capability to preferentially bind to the hydrophobic regions near loop2. Thus, lanosterol acts as a "water blocker" to prevent the invasion of solvent molecules into the hydrophobic core. These findings provide some valuable insights into the development of potential lanosterol-based drugs for cataract prevention and treatment.

Biotransformation of rare earth oxide nanoparticles eliciting microbiota imbalance.

BACKGROUND: Disruption of microbiota balance may result in severe diseases in animals and phytotoxicity in plants. While substantial concerns have been raised on engineered nanomaterial (ENM) induced hazard effects (e.g., lung inflammation), exploration of the impacts of ENMs on microbiota balance holds great implications. RESULTS: This study found that rare earth oxide nanoparticles (REOs) among 19 ENMs showed severe toxicity in Gram-negative (G-) bacteria, but negligible effects in Gram-positive (G+) bacteria. This distinct cytotoxicity was disclosed to associate with the different molecular initiating events of REOs in G- and G+ strains. La2O3 as a representative REOs was demonstrated to transform into LaPO4 on G- cell membranes and induce 8.3% dephosphorylation of phospholipids. Molecular dynamics simulations revealed the dephosphorylation induced more than 2-fold increments of phospholipid diffusion constant and an unordered configuration in membranes, eliciting the increments of membrane fluidity and permeability. Notably, the ratios of G-/G+ reduced from 1.56 to 1.10 in bronchoalveolar lavage fluid from the mice with La2O3 exposure. Finally, we demonstrated that both IL-6 and neutrophil cells showed strong correlations with G-/G+ ratios, evidenced by their correlation coefficients with 0.83 and 0.92, respectively. CONCLUSIONS: This study deciphered the distinct toxic mechanisms of La2O3 as a representative REO in G- and G+ bacteria and disclosed that La2O3-induced membrane damages of G- cells cumulated into pulmonary microbiota imbalance exhibiting synergistic pulmonary toxicity. Overall, these findings offered new insights to understand the hazard effects induced by REOs.

Double-Exchange-Induced in situ Conductivity in Nickel-Based Oxyhydroxides: An Effective Descriptor for Electrocatalytic Oxygen Evolution.

Motivated by in silico predictions that Co, Rh, and Ir dopants would lead to low overpotentials to improve OER activity of Ni-based hydroxides, we report here an experimental confirmation on the altered OER activities for a series of metals (Mo, W, Fe, Ru, Co, Rh, Ir) doped into γ-NiOOH. The in situ electrical conductivity for metal doped γ-NiOOH correlates well with the trend in enhanced OER activities. Density functional theory (DFT) calculations were used to rationalize the in situ conductivity of the key intermediate states of metal doped γ-NiOOH during OER. The simultaneous increase of OER activity with intermediate conductivity was later rationalized by their intrinsic connections to the double exchange (DE) interaction between adjacent metal ions with various d orbital occupancies, serving as an indicator for the key metal-oxo radical character, and an effective descriptor for the mechanistic evaluation and theoretical guidance in design and screening of efficient OER catalysts.

Molcontroller: A VMD Graphical User Interface Featuring Molecule Manipulation.

Visual Molecular Dynamics (VMD) is one of the most widely used molecular graphics software in the community of theoretical simulations. So far, however, it still lacks a graphical user interface (GUI) for molecular manipulations when doing some modeling tasks. For instance, translation or rotation of a selected molecule(s) or part(s) of a molecule currently only can be achieved using tcl scripts. Here, we use the Tcl/Tk toolkit to develop a user-friendly GUI for VMD, named Molcontroller, which is featured by allowing users to quickly and conveniently perform various molecular manipulations. This GUI might be helpful for improving the modeling efficiency of VMD users.

Molecular Origin of the Stability Difference in Four Shark IgNAR Constant Domains.

Improving the stability of antibodies for manufacture and shelf life is one of the main focuses of antibody engineering. One stabilization strategy is to perform specific mutations in human antibodies based on highly stable antibodies in other species. To identify the key residues for mutagenesis, it is necessary to understand the roles of these residues in stabilizing the antibody. Here, we use molecular dynamics simulations to study the molecular origin of the four shark immunoglobulin new antigen receptors constant domains (C1-C4). According to the unfolding pathways and the conformational free energy surfaces in 8 M urea at 380 K, the C2 domain is the most stable, followed by C4, C1, and C3, which agrees with the experimental findings. The C1 and C3 domains follow a common unfolding pathway in which the unfolding starts from the edge strands, particularly strand g, and then gradually progresses to the inner strands. Detailed structural analysis of the C2 domain reveals a "sandwich-like" R339-E322-R341 salt-bridge cluster on strand g, which grants ultrahigh stability to the C2 domain. We further design two sets of mutations by mutating E322 to alanine or setting all atomic charges in E322 to zero to break the salt-bridge cluster in the C2 domain, which confirms the importance of the salt bridges in stability. In the C4 domain, the D80-K104 salt bridge on strand g also strengthens the stability. On the other hand, in the C1 and C3 domains, there is no salt bridge on strand g. In addition to the salt bridges, the overall hydrophobicity score of the hydrophobic core is also positively correlated with the domain stability. Our findings provide a detailed microscopic picture of the molecular origin of the four shark immunoglobulin new antigen receptors constant domains that not only explains the differences in their structural stability but also provides important insights into future antibody design.

Potential blockade of the human voltage-dependent anion channel by MoS2 nanoflakes.

Despite significant interest in molybdenum disulfide (MoS2) nanomaterials, particularly in biomedicine, their biological effects have been understudied. Here, we explored the effect of MoS2 nanoflakes on the ubiquitous mitochondrial porin voltage-dependent anion channel (VDAC1), using a combined computational and functional approach. All-atomic molecular dynamics simulations suggest that MoS2 nanoflakes make specific contact interactions with human VDAC1. We show that the initial contacts between hVDAC1 and the nanoflake are hydrophobic but are subsequently enhanced by a complex interplay of van der Waals (vdW), hydrophobic and electrostatic interactions in the equilibrium state. Moreover, the MoS2 nanoflake can insert into the lumen of the hVDAC1 pore. Free-energy calculations computed by the potential of mean force (PMF) verify that the blocked configuration of the MoS2-hVDAC1 complex is more energetically favorable than the non-blocked binding mode. Consistent with these predictions, we showed that MoS2 depolarizes the mitochondrial membrane potential (Ψm) and causes a decrease in the viability of mammalian tissue culture cells. These findings might shed new light on the potential biological effect of MoS2 nanomaterials.

Different protonated states at the C-terminal of the amyloid-ß peptide modulate the stability of S-shaped protofibril.

Studies have found strong correlations between polymorphism and structural variations in amyloid-ß (Aß) fibrils and the diverse clinical subtypes of Alzheimer's disease (AD). Thus, a detailed understanding of the conformational behavior of Aß fibrils may be an aid to elucidate the pathological mechanisms involved in AD. However, a key point that has been inadvertently underestimated or dismissed is the role of the protonated state at the C-terminal residue of amyloid-ß peptides, which can give rise to intrinsic differences in the morphology and stability of the fibrils. For instance, the effects of the salt bridge formed between the C-terminal residue A42 and the residue K28 on the S-shaped Aß protofibril structure remain unknown and may be different from those in the U-shaped Aß protofibril structures. To address this effect, we explore the stability of the S-shaped protofibrils capped with different C-terminal modifications, including carboxyl group in its deprotonated (COO-) and protonated (COOH) states, by using molecular dynamics simulations. Our findings indicated that the C-terminal deprotonated protofibril is significantly more stable than its C-terminal protonated counterpart due to a well-defined and highly stable zipper-like salt-bridge-chain formed by the ε-NH3 + groups on the sidechain of residue K28 and the C-terminal COO- group at the A42 residue. The revealed underlying molecular mechanism for the different stability of the protofibrils provides insights into the diversity of polymorphism in Aß fibrils.

Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular dynamics study.

Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids, which has shown promising applications in lowering Aß peptide neurotoxicity in vitro by preventing aggregation of Aß peptides and relieving accumulation of Aß fibrils. Unfortunately, the underlying molecular mechanisms of how DHA interferes with the aggregation of Aß peptides remain largely enigmatic. Herein, aggregation behaviors of amyloid-ß(Aß)16-21 peptides (KLVFFA) with or without the presence of a DHA molecule were comparatively studied using extensive all-atom molecular dynamics simulations. We found that DHA could effectively suppress the aggregation of KLVFFA peptides by redirecting peptides to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made it randomly but tightly entangled with Leu-17, Phe-19, and Phe-20 residues to form unstructured but stable complexes. These lower-ordered unstructured oligomers could eventually pass through energy barriers to form ordered ß-sheet structures through large conformational fluctuations. This study depicts a microscopic picture for understanding the role and mechanism of DHA in inhibition of aggregation of Aß peptides, which is generally believed as one of the important pathogenic mechanisms of Alzheimer's disease.

High-Throughput Computational Screening of Two-Dimensional Covalent Organic Frameworks (2D COFs) for Capturing Radon in Moist Air.

Radon (Rn) and its decay products are the primary sources of natural ionizing radiation exposure for the public, posing significant health risks, including being a leading cause of lung cancer. Porous material-based adsorbents offer a feasible and efficient solution for controlling Rn concentrations in various scenes to achieve safe levels. However, due to competitive adsorption between Rn and water, finding candidates with a higher affinity and capacity for capturing Rn in humid air remains a significant challenge. Here, we conducted high-throughput computational screening of 8641 two-dimensional covalent organic frameworks (2D COFs) in moist air using grand canonical Monte Carlo simulations. We identified the top five candidates and revealed the structure-performance relationship. Our findings suggest that a well-defined cavity with an approximate spherical inner space, with a diameter matching that of Rn, is the structural basis for a proper Rn capturing site. This is because the excellent steric match between the cavity and Rn maximizes their van der Waals dispersion interactions. Additionally, the significant polarization electrostatic potential surface of the cavity can regulate the adsorption energy of water and ultimately impact Rn selectivity. Our study offers a potential route for Rn management using 2D COFs in moist air and provides a scientific basis for further experimentation.

Spinel-Derived Formation and Amorphization of Bimetallic Oxyhydroxides for Efficient Electrocatalytic Biomass Oxidation.

Replacing the oxygen evolution reaction (OER) with water-assisted oxidation of organic molecules represents a promising approach for achieving sustainable electrochemical biomass utilization. Among numerous OER catalysts, spinels have received substantial attention due to their manifold compositions and valence states, yet their application in biomass conversions remains rare. Herein, a series of spinels were investigated for the selective electrooxidation of furfural and 5-hydroxymethylfurfural, two model substrates for versatile value-added chemical products. Spinel sulfides universally exhibit superior catalytic performance compared to that of spinel oxides, and further investigations show that the replacement of oxygen with sulfur led to the complete phase transition of spinel sulfides into amorphous bimetallic oxyhydroxides during electrochemical activation, serving as the active species. Excellent values of conversion rate (100%), selectivity (100%), faradaic efficiency (>95%), and stability were achieved via sulfide-derived amorphous CuCo-oxyhydroxide. Furthermore, a volcano-like correlation was established between their BEOR and OER activities based on an OER-assisted organic oxidation mechanism.

The Critical Role of Initial/Operando Oxygen Loading in General Bismuth-Based Catalysts for Electroreduction of Carbon Dioxide.

Operando reconstruction of solid catalyst into a distinct active state frequently occurs during electrocatalytic processes. The correlation between initial and operando states, if ever existing, is critical for the understanding and precise design of a catalytic system. Inspired by recently established intermediate metallic state of Bi-based catalysts during electrocatalytic carbon dioxide reduction (CO2RR), here we investigate a series of Bi oxide catalysts (Bi, Bi2O3, BiO2) and demonstrate that the operando surface/subsurface oxygen loading, positively correlated to the initial oxygen content, plays a critical role in determining Bi-based CO2RR performance. Higher initial oxygen loading indicates a better electrocatalytic efficiency. Further analysis shows that this conclusion generally applies to all Bi-based electrocatalysts reported up to date. Following this principle, cost-effective BiO2 nanocrystals demonstrated the highest formate Faradaic efficiency (FE) and current density compared to Bi/Bi2O3, further allowing a pair-electrolysis system with 800 mA/cm2 current density and an overall 175% FE for formate production.

The Molecular Mechanism of Human Voltage-Dependent Anion Channel 1 Blockade by the Metallofullerenol Gd@C82(OH)22: An In Silico Study.

The endohedral metallofullerenol Gd@C82(OH)22 has been identified as a possible antineoplastic agent that can inhibit both the growth and metastasis of cancer cells. Despite these potentially important effects, our understanding of the interactions between Gd@C82(OH)22 and biomacromolecules remains incomplete. Here, we study the interaction between Gd@C82(OH)22 and the human voltage-dependent anion channel 1 (hVDAC1), the most abundant porin embedded in the mitochondrial outer membrane (MOM), and a potential druggable target for novel anticancer therapeutics. Using in silico approaches, we observe that Gd@C82(OH)22 molecules can permeate and form stable interactions with the pore of hVDAC1. Further, this penetration can occur from either side of the MOM to elicit blockage of the pore. The binding between Gd@C82(OH)22 and hVDAC1 is largely driven by long-range electrostatic interactions. Analysis of the binding free energies indicates that it is thermodynamically more favorable for Gd@C82(OH)22 to bind to the hVDAC1 pore when it enters the channel from inside the membrane rather than from the cytoplasmic side of the protein. Multiple factors contribute to the preferential penetration, including the surface electrostatic landscape of hVDAC1 and the unique physicochemical properties of Gd@C82(OH)22. Our findings provide insights into the potential molecular interactions of macromolecular biological systems with the Gd@C82(OH)22 nanodrug.

Molecular Dynamics Simulation Study on Interactions of Cycloviolacin with Different Phospholipids.

Cyclotides are disulfide-rich cyclic peptides isolated from plants, which are extremely stable against thermal and proteolytic degradation, with a variety of biological activities including antibacterial, hemolytic, anti-HIV, and anti-tumor. Most of these bioactivities are related to their preference for binding to certain types of phospholipids and subsequently disrupt lipid membranes. In the present study, we use a cyclotide, cycloviolacin O2 (cyO2), as a model system to investigate its interactions with three lipid bilayers 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG)-doped POPE, and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), to help understand its potential mechanism of action toward the membranes at the molecular level using molecular dynamics simulations. In our simulations, cyO2 repeatedly forms stable binding complexes with the POPE-containing bilayers, while within the same simulation time scale, it "jumps" back and forth on the surface of the POPC bilayer without a strong binding. Detailed analyses reveal that the electrostatic attraction is the main driving force for the initial bindings between cyO2 and the lipids, but with strikingly different strengths in different bilayers. For the POPE-containing bilayers, the charged residues of cyO2 attract both POPE amino and phosphate head groups favorably; meanwhile, its hydrophobic residues are deeply inserted into the lipid hydrophobic tails (core) of the membrane, thus forming stable binding complexes. In contrast, POPC lipids with three methyl groups on the amino head group create a steric hindrance when interacting with cyO2, thus resulting in a relatively difficult binding of cyO2 on POPC compared to POPE. Our current findings provide additional insights for a better understanding of how cyO2 binds to the POPE-containing membrane, which should shed light on the future cyclotide-based antibacterial agent design.