Atomic-level Understanding Research Articles

Oxygen evolution reaction mechanism on platinum dioxide surfaces based on density functional theory calculations

The oxygen evolution reaction (OER) counterbalances the hydrogen evolution reaction (HER) during water dissociation under an electric field. Platinum (Pt) group metals and their oxides exhibit considerable durability as electrocatalysts for water dissociation. However, an atomic-level understanding of the OER on Pt-oxide surfaces at high potential remains elusive because of the limited experimental techniques for tracking dynamic surface species involved in adsorption, electron transfer, or interactions. Herein, the OER mechanisms involving water nucleophilic attack (WNA) and intramolecular oxygen coupling (IMOC) were studied on Pt and platinum dioxide (PtO2) surfaces using density functional theory (DFT) calculations, indicating that the WNA mechanism dominates the OER on Pt and PtO2 electrode surfaces. The OER activity on the PtO2(100) surface is better than the PtO2(111) surface due to the high overpotential obtained on PtO2(111). These findings offer valuable insights into the OER mechanism on oxidized Pt surfaces and suggest new strategies for designing and optimizing Pt-based catalysts for improved stability and performance.

In‐Situ Pt‐Decorated, Direct Growth of Mixed Phase 2H/1T–MoSe2 on Carbon Paper for Enhanced Hydrogen Evolution Reaction

Metal dichalcogenide‐based 2D materials, gained considerable attention recently as a hydrogen evolution reaction (HER) electrocatalyst. In this work, we synthesized MoSe2‐based electrocatalyst via hydrothermal route with varying phase contents (1T/2H) and respective HER performances were evaluated under the acidic media (0.5 m H2SO4), where best HER performance was obtained from the sample consisting of mixed 1T/2H phases, which was directly grown on a carbon paper (167 mV at 10 mA cm−2) Furthermore, HER performance of electrocatalyst was further improved by in‐situ electrodeposition of Pt nanoparticles (0.15 wt%) on the MoSe2 surface, which lead to significant enhancement in the HER performances (133 mV at 10 mA cm−2). Finally, we conducted density functional theory calculations to reveal the origin of such enhanced performances when the mixed 1T/2H phases were present, where phase boundary region (1T/2H heterojunction) act as a low energy pathway for H2 adsorption and desorption via electron accumulation effect. Moreover, presence of the Pt nanoparticles tunes the electronic states of the MoSe2 based catalyst, resulting in the enhanced HER activity at heterointerface of 1T/2H MoSe2 while facilitating the hydrogen adsorption and desorption process providing a low energy pathway for HER. These results provide new insight on atomic level understanding of the MoSe2 based catalyst for HER application.

Highly Selective Electroreduction of Carbon Dioxide Using Defect-Driven Catalysis.

The production of methanol from the electrochemical reduction of CO2 is a promising method of mitigating climate change while simultaneously producing a useful liquid fuel. In this study, we design self-assembled monolayers (SAMs) of thiols on metal and metal oxide electrodes that operate via cooperative catalysis between the thiolated surface sites and exposed electrode defect sites. This defect-driven mechanism enables the fabrication of SAM-modified ZnO electrodes that yield methanol with an extraordinarily high Faradaic efficiency of up to 92%. To understand the origin of this high selectivity, we study the effect of the chain length of the alkanethiols, different tail functional groups, and applied voltages on catalyst performance. These results combined with density functional theory calculations give a detailed atomic-level understanding of catalyst operation. Furthermore, the SAM linkage tolerates CO2 reduction conditions, and the catalyst's excellent selectivity for methanol remains high after 10 h of continuous conversion. Taken together, these findings with SAM-based electrodes convey a new and facile design strategy for the creation of highly selective CO2 reduction electrocatalysts.

Activation of the Influenza B M2 Proton Channel (BM2).

Influenza B viruses have cocirculated during most seasonal flu epidemics and can cause significant human morbidity and mortality due to their rapid mutation, emerging drug resistance, and severe impact on vulnerable populations. The influenza B M2 proton channel (BM2) plays an essential role in viral replication, but the mechanisms behind its symmetric proton conductance and the involvement of a second histidine (His27) cluster remain unclear. Here we performed membrane-enabled continuous constant-pH molecular dynamics simulations on wildtype BM2 and a key H27A mutant channel to explore its pH-dependent conformational switch. Simulations captured the activation as the first histidine (His19) protonates and revealed the transition at lower pH values compared to AM2 is a result of electrostatic repulsions between His19 and preprotonated His27. Crucially, we provided an atomic-level understanding of the symmetric proton conduction by identifying preactivating channel hydration in the C-terminal portion. This research advances our understanding of the function of BM2 function and lays the groundwork for further chemically reactive modeling of the explicit proton transport process as well as possible antiflu drug design efforts.

Fabrication of B-C-N nanosheets on Rh(111) from benzene – borazine mixtures

Atomic level studies of solid state surfaces performed in ultra-high vacuum (UHV) had already an energetic 15–20 years past when our research group in Szeged started working in this field in mid 1970s. Till then several very important methods had been developed, like UHV technology, commercially available electron and photoelectron spectroscopy techniques, etc. Characterization of metal and semiconductor (oxide) surfaces and their adsorption properties had already been widely studied. In any case, the last 40–50 years also witnessed great discoveries and exciting new techniques. Considering only the activity related to heterogeneous catalysis, the main focus of our research group, new breakthrough methods emerged like HREELS, RAIRS, SPM, NAPXPS, EXAFS, NEXAFS. Along this path, new experimental and theoretical approaches appeared like planar model catalysts and inverse catalysts, atomic level investigation and understanding of surface diffusion-controlled phenomena (particle growth and disruption, strong metal-support interaction (SMSI), decoration, spillover), atomic level identification of active sites, self-organized nano-systems, surface alloys and nanotemplates. It was great to participate in this magical activity for more than 50 years. Both internationally and locally in Szeged, in the last two decades, surface science has opened to the wide world of 2D materials like the semimetal graphene and the insulator hexagonal boron nitride. However, the formation of a mixed layer of C, B and N proved to be a difficult task due to the primary tendency for phase separation. In the present work, we report on a preparation method of honeycomb “BCN” materials on Rh(111) by using benzene/borazine mixtures as precursors. It was demonstrated that by a suitable choice of the growth parameters, the formation of large, separated graphene and h-BN islands can be avoided.

Study on the mechanism of crystal-induced plasticity enhancement in Ni-Zr crystal/amorphous composites by molecular dynamics simulation

The industrial applications of metallic glass (MGs) are limited by poor plasticity, which crystal/amorphous composites (CACs) can effectively address. This study simulates the compression of Ni-Zr MGs with embedded fcc crystal phases by molecular dynamics to elucidate the mechanism of crystal-induced plasticity enhancement. The plasticity of CACs improves with larger crystal sizes. Atoms at the crystal-amorphous interfaces (CAIs) are classified as CAIfcc and CAIMGs for fcc and MGs, respectively. The transformation of CAIfcc to CAIMGs at the CAIs is crucial for plastic flow during compression. The connection between CAIfcc and CAIMGs clusters is less stable than that of fcc, making it more prone to damage and leading to multiple shear bands (SBs). These SBs offer additional pathways for plastic flow, reducing stress concentration and enhancing material plasticity. This research provides an atomic-level understanding of crystal-induced plasticity in CACs, offering valuable insights for designing high-performance CACs.

Quantum Simulations of Radiation Damage in a Molecular Polyethylene Analog.

An atomic-level understanding of radiation-induced damage in simple polymers like polyethylene is essential for determining how these chemical changes can alter the physical and mechanical properties of important technological materials such as plastics. Ensembles of quantum simulations of radiation damage in a polyethylene analog are performed using the Density Functional Tight Binding method to help bind its radiolysis and subsequent degradation as a function of radiation dose. Chemical degradation products are categorized with a graph theory approach, and occurrence rates of unsaturated carbon bond formation, crosslinking, cycle formation, chain scission reactions, and out-gassing products are computed. Statistical correlations between product pairs show significant correlations between chain scission reactions, unsaturated carbon bond formation, and out-gassing products, though these correlations decrease with increasing atom recoil energy. The results present relatively simple chemical descriptors as possible indications of network rearrangements in the middle range of excitation energies. Ultimately, the work provides a computational framework for determining the coupling between nonequilibrium chemistry in polymers and potential changes to macro-scale properties that can aid in the interpretation of future radiation damage experiments on plasticmaterials.

Vertically oriented low-dimensional perovskites for high-efficiency wide band gap perovskite solar cells

Controlling crystal growth alignment in low-dimensional perovskites (LDPs) for solar cells has been a persistent challenge, especially for low-n LDPs (n < 3, n is the number of octahedral sheets) with wide band gaps (>1.7 eV) impeding charge flow. Here we overcome such transport limits by inducing vertical crystal growth through the addition of chlorine to the precursor solution. In contrast to 3D halide perovskites (APbX3), we find that Cl substitutes I in the equatorial position of the unit cell, inducing a vertical strain in the perovskite octahedra, and is critical for initiating vertical growth. Atomistic modelling demonstrates the thermodynamic stability and miscibility of Cl/I structures indicating the preferential arrangement for Cl-incorporation at I-sites. Vertical alignment persists at the solar cell level, giving rise to a record 9.4% power conversion efficiency with a 1.4 V open circuit voltage, the highest reported for a 2 eV wide band gap device. This study demonstrates an atomic-level understanding of crystal tunability in low-n LDPs and unlocks new device possibilities for smart solar facades and indoor energy generation.

Promoting effect of CO2 on NiCr oxidation: Atomistic origins based on first principles.

The adsorption and dissociation of CO2 on both perfect and oxygen-deficient α-Cr2O3 (0001) surfaces, alongside the subsequent incorporation of the resulting C into the oxide lattice and its impact on oxide growth, are investigated using first-principles calculations. Our findings reveal that oxygen vacancies significantly enhance CO2 adsorption and promote its stepwise decomposition into C and O atoms. The resulting C can spontaneously dissolve into the oxide lattice through the oxygen vacancies. The presence of bulk dissolved C in the Cr2O3 lattice substantially enhances the formation, migration, and clustering of oxygen vacancies in the bulk. These results provide an atomic-level understanding of how CO2 accelerates the oxidation of chromia-forming alloys, offering microscopic insights for controlling oxide growth and mitigating oxidation-induced degradation of high-temperature alloys.

Co-effect of perchlorate anions and hydrated protons on the electrochemical formation of Adams’ catalyst

The structure and morphology of oxide on the metal electrodes are strongly linked with the activity and stability of the electrocatalysts. Herein, the novel co-effect of anion and hydrated proton on structure of PtO2 formation is observed during the oxidation of water on Pt(100) preferentially oriented nanoparticles with in situ Raman spectroscopy and XPS. Higher concentrations (≥1.5 M) of non-specifically adsorbed perchlorate in 0.1 M perchloric acid solution facilitated the formation of crystalline α−PtO2 during the electro−oxidation of Pt(100), and no crystalline α−PtO2 was obtained without acid. Higher acidity electrolyte solution favors the formation of crystalline α–PtO2, indicating that proton plays a key role since specifically adsorbed sulfate without sulfuric acid did not lead to the formation of crystalline α–PtO2. A model containing anions, protons, and water molecules co-adsorbed on the Pt surface is constructed during density functional theory (DFT) calculations, which well explains the formation of crystalline α–PtO2 depending on anion and proton. The study findings provide an alternate approach for environmentally friendly and controllable preparation of Adams’ catalyst and an atomic–level understanding of oxide formation on Pt electrodes, which is essential for developing the next–generation electro-catalyst with exceptional performance and stability.

Mechanisms of Controllable Growth and Ohmic Contact of Two-Dimensional Molybdenum Disulfide: Insight from Atomistic Simulations.

ConspectusTwo-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs), in particular molybdenum disulfide (MoS2), have recently attracted huge interest due to their proper bandgap, high mobility at 2D limit, and easy-to-integrate planar structure, which are very promising for extending Moore's law in postsilicon electronics technology. Great effort has been devoted toward such a goal since the demonstration of protype MoS2 devices with high room-temperature on/off current ratios, ultralow standby power consumption, and atomic level scaling capacity down to sub-1-nm technology node. However, there are still several key challenges that need to be addressed prior to the real application of MoS2-based electronics technology. The controllable growth of wafer-scale single-crystal MoS2 on industry-compatible insulating substrates is the prerequisite of application while the currently synthesized MoS2 films mostly are polycrystalline with limited sizes of single-crystal domains and may involve metal substrates. The precise layer-control is also very important for MoS2 growth since its electronic properties are layer-dependent, whereas the layer-by-layer growth of multilayer MoS2 dominated by the van der Waals (vdW) epitaxy leads to poor thickness uniformity and noncontinuously distributed domains. High density up to 1013 cm-2 of sulfur vacancies (SVs) in grown MoS2 can cause unfavorable carrier scatting and electronic properties variations and will inevitably disturb the device performance. The dangling-bond-free surface of MoS2 gives rise to an inherent vdW gap at metal-semiconductor (M-S) contact, which leads to high electrical resistance and poor current-delivery capability at the contact interface and thereby substantially limits the performances of MoS2 devices.In this Account, we briefly review recent experimental and theoretical attempts for addressing the aforementioned challenges and present our own insights from atomistic simulations. We theoretically revealed the vital role of substrate steps for guiding unidirectional nucleation of monolayer MoS2 and uniform nucleation and edge-aligned growth of bilayer MoS2 by advanced simulations. The established thermodynamic mechanisms have successfully directed the experimental works on the controllable growth of 2 in. single-crystal monolayer and centimeter-scale uniform bilayer MoS2. The postgrowth repair mechanism of SV defect in MoS2 via thiol chemistry treatment has been theoretically explored with the consideration of side reaction of surface functionalization to help experimentally reduce SV defect density by 75%. Beyond the atomic level understanding, theoretical simulations proposed the electronic states hybridization mechanism across the semimetal-MoS2 vdW interface, thereby guiding experimental effort for realizing Ohmic contact at the MoS2-Sb(0112) vdW interface with record-low contact resistance.These advances provide a sound basis with an atomic-level understanding for addressing the related issues. However, there are still notable gaps in terms of system size and time scale of dynamics between atomistic simulations and experimental observations for the studies of MoS2 growth and interfaces. The combination of multiscale simulations and artificial intelligence technology is expected to narrow these gaps and provide a more insightful understanding of the controllable growth and interfacial properties modulation of MoS2. We conclude the Account with the standing challenges and outlook on future research directions from the theoretical perspective.

The role of crystallographic orientation on surface properties and ion transport in lithium germanate (Li2GeO3) anodes: A computational approach

The performance of lithium-ion batteries (LIBs) hinges on the surface properties of their anodes. Compared to the bulk material, the anode surface is more susceptible to environmental changes during lithium (Li) intake and release, directly impacting factors like capacity, cycling stability, and charge/discharge rates. Lithium germanate (Li2GeO3, LGO) has emerged as a promising anode material due to its fast Li-ion conduction. While numerous studies have explored performance improvements through various methods, including defect engineering. However, there is currently a lack of atomistic-level understanding of the surface structure. Consequently, despite the importance of precisely understanding the surface to manipulate its different properties, specific surface details of LGO remain unclear. This knowledge gap hinders precise manipulation of surface properties for optimal performance.This study addresses this critical need by employing theoretical calculations to predict the structural, electrochemical characteristics, and Li-ion transport behavior in LGO surfaces. Our results indicate that polar surfaces exhibit lower formation energies compared to non-polar surfaces. Further investigation revealed that Li-terminated surfaces possess the lowest surface energy among various surface terminations. Interestingly, the work function calculations displayed an opposite trend to surface formation energy, with polar surfaces exhibiting the lowest work function values.To explore Li-ion transport, we employed ab initio molecular dynamics simulations. Notably, the (003) surface displayed the highest Li-ion diffusion rate among all considered surfaces.Further analysis of the (001) surface, which exhibited similar diffusion pathways to the (003) surface, revealed a lower diffusion rate.To understand this disparity, nudged elastic band (NEB) simulations were used to estimate the energy barriers for Li-ion migration along each pathway in both structures. Despite sharing similar pathways, the energy barriers in the (003) surface were significantly lower than those in the (001) surface. This finding suggests that the intrinsic energy landscape of the surface plays a crucial role in dictating Li-ion transport behavior.

Unraveling the Dynamic Properties of New-Age Energy Materials Chemistry Using Advanced In Situ Transmission Electron Microscopy.

The field of energy storage and conversion materials has witnessed transformative advancements owing to the integration of advanced in situ characterization techniques. Among them, numerous real-time characterization techniques, especially in situ transmission electron microscopy (TEM)/scanning TEM (STEM) have tremendously increased the atomic-level understanding of the minute transition states in energy materials during electrochemical processes. Advanced forms of in situ/operando TEM and STEM microscopic techniques also provide incredible insights into material phenomena at the finest scale and aid to monitor phase transformations and degradation mechanisms in lithium-ion batteries. Notably, the solid-electrolyte interface (SEI) is one the most significant factors that associated with the performance of rechargeable batteries. The SEI critically controls the electrochemical reactions occur at the electrode-electrolyte interface. Intricate chemical reactions in energy materials interfaces can be effectively monitored using temperature-sensitive in situ STEM techniques, deciphering the reaction mechanisms prevailing in the degradation pathways of energy materials with nano- to micrometer-scale spatial resolution. Further, the advent of cryogenic (Cryo)-TEM has enhanced these studies by preserving the native state of sensitive materials. Cryo-TEM also allows the observation of metastable phases and reaction intermediates that are otherwise challenging to capture. Along with these sophisticated techniques, Focused ion beam (FIB) induction has also been instrumental in preparing site-specific cross-sectional samples, facilitating the high-resolution analysis of interfaces and layers within energy devices. The holistic integration of these advanced characterization techniques provides a comprehensive understanding of the dynamic changes in energy materials. This review highlights the recent progress in employing state-of-the-art characterization techniques such as in situ TEM, STEM, Cryo-TEM, and FIB for detailed investigation into the structural and chemical dynamics of energy storage and conversion materials.

Exploring the dynamic evolution of lattice oxygen on exsolved-Mn2O3@SmMn2O5 interfaces for NO Oxidation

Lattice oxygen in metal oxides plays an important role in the reaction of diesel oxidation catalysts, but the atomic-level understanding of structural evolution during the catalytic process remains elusive. Here, we develop a Mn2O3/SmMn2O5 catalyst using a non-stoichiometric exsolution method to explore the roles of lattice oxygen in NO oxidation. The enhanced covalency of Mn–O bond and increased electron density at Mn3+ sites, induced by the interface between exsolved Mn2O3 and mullite, lead to the formation of highly active lattice oxygen adjacent to Mn3+ sites. Near-ambient pressure X-ray photoelectron and absorption spectroscopies show that the activated lattice oxygen enables reversible changes in Mn valence states and Mn-O bond covalency during redox cycles, reducing energy barriers for NO oxidation and promoting NO2 desorption via the cooperative Mars-van Krevelen mechanism. Therefore, the Mn2O3/SmMn2O5 exhibits higher NO oxidation activity and better resistance to hydrothermal aging compared to a commercial Pt/Al2O3 catalyst.

Effects of intergranular hydride precipitation on the mechanical behavior of bicrystalline zirconium: A molecular dynamics-based study

This article investigated the impact of intergranular hydride precipitation on the mechanical behavior of zirconium (Zr) bi-crystals using molecular dynamics (MD)-based simulations. Uniaxial tensile tests were conducted to explore the effects of hydride precipitation on symmetric and asymmetrical tilt grain boundaries (GBs) of Zr with [0 1‾ 10] as the tilt axis. The stress-strain curves and deformation governing mechanism of bi-crystalline Zr were analyzed using the MD-based simulations in conjunction with the COMB force field. Misfit stress and tensile stress degradation induced by hydride precipitation were evaluated to understand their correlation with GB misorientation angles. Hydride precipitation induced the residual stresses in the vicinity of GB plane and mitigates the overall mechanical properties. It was predicted from the simulations that GBs with low misfit stress develop a lower mismatch between the lattice of Zr and hydride precipitate. Consequently, the effect of hydride on the tensile strength gets nullify. In contrast, the effects of hydrides are more pronounced on the tensile strength of Zr containing low-energy GBs in conjunction with high-misfit stress. The study further reveals that intergranular hydride precipitation causes the hydride embrittlement effect in Zr bicrystals, which intensifies with large size hydride precipitate. These findings contribute to an atomistic-level understanding of intergranular hydride-induced embrittlement and its correlation with Zr grain boundary orientation.

Relationship between Structural Defects and Free Electrons in Icosahedral Nanoclusters.

According to the classic superatom model, metal nanoclusters with a "magic number" of free valence electrons display high stability, manifesting as the closed-shell-dependent electronic robustness. The icosahedral nanobuilding blocks containing eight free electrons were the most common in constructing metal nanoclusters; however, the structure defect-dependent variations of the free electron count in icosahedral configurations are still far from thorough research. Here, we reported a hydride-containing [Pt2Ag15(SAdm)4(DPPOE)4H]2+ nanocluster with two largely defective Pt1Ag8 icosahedral cores. Together with previously reported complete or slightly defective icosahedra in metal nanoclusters, the largely defective Pt1Ag8 core provided important clues to reveal the evolutionary mode of structural defects and free electrons in icosahedral nanoclusters; the free electron count of icosahedron was reduced two-by-two (i.e., from 8e to 6e and then to 4e) accompanied by the structure defection. Overall, the work presented a novel Pt2Ag15 nanocluster with a largely defective core structure that enables an atomic-level understanding of the relationship between structural defects and free electrons in icosahedral nanoclusters.

Atomic structures of a bacteriocin targeting Gram-positive bacteria

Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube. Compared to contractile machines targeting Gram-negative bacteria, major differences reside in the baseplate and contraction magnitude, consistent with target envelope differences. The multifunctional hub-hydrolase protein connects the tube and baseplate and is positioned to degrade peptidoglycan during penetration. The full-length tape measure protein forms a coiled-coil helix bundle homotrimer spanning the entire diffocin. Our study offers mechanical insights and principles for designing potent protein-based precision antibiotics.

(De)sodiation Mechanism of Bi2MoO6 in Na-Ion Batteries Probed by Quasi-Simultaneous Operando PDF and XAS.

Operando characterization can reveal degradation processes in battery materials and are essential for the development of battery chemistries. This study reports the first use of quasi-simultaneous operando pair distribution function (PDF) and X-ray absorption spectroscopy (XAS) of a battery cell, providing a detailed, atomic-level understanding of the cycling mechanism of Bi2MoO6 as an anode material for Na-ion batteries. This material cycles via a combined conversion-alloying reaction, where electrochemically active, nanocrystalline Na x Bi particles embedded in an amorphous Na-Mo-O matrix are formed during the first sodiation. The combination of operando PDF and XAS revealed that Bi obtains a positive oxidation state at the end of desodiation, due to formation of Bi-O bonds at the interface between the Bi particles and the Na-Mo-O matrix. In addition, XAS confirmed that Mo has an average oxidation state of +6 throughout the (de)sodiation process and, thus, does not contribute to the capacity. However, the local environment of Mo6+ changes from tetrahedral coordination in the desodiated state to distorted octahedral in the sodiated state. These structural changes are linked to the poor cycling stability of Bi2MoO6, as flexibility of this matrix allows movement and coalescence of the Na x Bi particles, which is detrimental to the electrochemical stability.

First-Principles Structure Search Study of 17-β-Estradiol Adsorption on Graphene.

17-Beta-estradiol (E2), a steroid hormone synthesized from cholesterol, has various impacts on health and the environment. Currently, the gold standard for its measurement in the body is a conventional blood test (mass spectrometry), but carbon-based electrochemical sensors have been proposed as an alternative due to their advantages, such as rapid analysis time and sensitivity. To improve the atomic-level understanding of the interactions at the substrate surface, we performed density functional theory (DFT) simulations to study the nature of the adsorption of E2 on pristine graphene. Bayesian Optimization Structure Search (BOSS) was employed to reduce human bias in the determination of the most favorable adsorption configurations. Two stable adsorption minimum configurations were found. Analysis of their electronic properties indicates that E2 physisorbs on graphene. Embarking upon complex carbonaceous materials, the importance of finding all possible minimum candidates with automated structure search tools is highlighted. Computational investigations facilitate tailoring substrate materials with outstanding performance and applications in neuroscientific research, fertility monitoring, and clinical trials. Combining them with experimental research carries significant potential to advance sensor design beyond the current state-of-the-art.

In silico analysis of aptamer-RNA conjugate interactions with human transferrin receptor

The human transmembrane protein Transferrin Receptor-1 is regarded as a promising target for the systemic delivery of therapeutic agents, particularly of nucleic acid therapeutics, such as short double stranded RNAs. This ubiquitous receptor is involved in cellular iron uptake, keeping intracellular homeostasis. It is overexpressed in multiple cancer cell types and is internalized via clathrin-mediated endocytosis. In previous studies, a human transferrin receptor-1 RNA aptamer, identified as TR14 ST1–3, was shown to be capable of effectively internalizing into cells in culture and to deliver small, double stranded RNAs in vitro and in vivo, via systemic administration.To understand, at the molecular level, the aptamer binding to the receptor and the impact of conjugation with the therapeutic RNA, a multi-level in silico protocol was employed, including protein-aptamer docking, molecular dynamics simulations and free energy calculations. The competition for the binding pocket, between the aptamer and the natural ligand human Transferrin, was also evaluated.The results show that the aptamer binds to the same region as Transferrin, with residues from the helical domain showing a critical role. Moreover, the conjugation to the therapeutic RNA, was shown not to affect aptamer binding. Overall, this study provides an atomic-level understanding of aptamer association to human Transferrin Receptor-1 and of its conjugation with a short model-therapeutic RNA, providing also important clues for futures studies aiming to deliver other oligonucleotide-based therapeutics via Transferrin Receptor.