Molecular Conformational Changes Research Articles

Reversible Isomerization of Stiff-Stilbene by an Oriented External Electric Field.

Understanding and effectively controlling molecular conformational changes are essential for developing responsive and dynamic molecular systems. Here, we report that an oriented external electric field (OEEF) is an effective catalyst for the cis-trans isomerization of stiff-stilbene, a key component of overcrowded alkene-based rotary motors. This reversible isomerization occurs under ambient conditions, is free from side reactions, and has been verified using ultraperformance liquid chromatography and UV-vis absorption spectroscopy. Low electric field promotes cis-to-trans conversion, and high electric field enables the reverse trans-to-cis process, demonstrating the precise reaction control through electric field manipulation. Density functional theory calculations reveal the mechanism of the electric-field-catalyzed cis-trans carbon-carbon double bond isomerization. Our findings provide a novel perspective on constructing OEEF-catalyzed, reversible molecular systems and pave the way for fully electrically driven artificial molecular machines.

Lipid droplet specific BODIPY based rotors with viscosity sensitivity to distinguish normal and cancer cells: impact of molecular conformation.

Lipid droplets (LDs) are dynamic, multifunctional organelles critical for regulating energy balance, cell signaling, membrane formation, and trafficking. Recent studies have highlighted LDs as emerging cancer biomarkers, with cancer cells typically exhibiting a higher number and viscosity of LDs compared to normal cells. This discovery paves the way for developing molecular probes that can monitor intracellular viscosity changes within LDs, offering a powerful tool for early cancer diagnosis, recurrence monitoring, and therapeutic interventions. In this study, we designed and synthesized two series of donor-acceptor (D-A) conjugated BODIPY-cyanostilbene based fluorophores (5a-c and 6a-c) by fine-tuning the cyanostilbene unit with three distinct substituents (OMe, H, Cl) and modulating the molecular conformation via rigidifying the indacene core. While the terminal substituents had a minimal effect on the optical properties, changes in molecular conformation significantly impacted the photophysical behavior of the fluorophores. Compounds 5a-c function as molecular rotors, with the free rotation of the meso-biphenyl rings leading to non-radiative deactivation of the excited state, resulting in weak emission. Additionally, this structural feature makes them highly responsive to changes in viscosity. As the glycerol concentration increased from 0% to 99%, the fluorescence intensity of compounds 5a, 5b, and 5c increased dramatically by 17-fold, 78-fold, and 43-fold, respectively. In contrast, compounds 6a-c, with restricted phenyl ring rotation due to tetra-methyls on the indacene unit, showed only a modest 2-3-fold increment in fluorescence intensity under similar conditions. These fluorophores possess several key advantages, including high selectivity for LDs, good photostability, sensitivity to viscosity, and responsiveness to polarity and pH. Moreover, they effectively differentiate between normal and cancer cells, making them valuable tools for cancer diagnosis and potential therapeutic applications.

Orientational Disorder and Molecular Correlations in Hybrid Organic-Inorganic Perovskites: From Fundamental Insights to Technological Applications.

Hybrid organic-inorganic perovskites (HOIP) have emerged in recent years as highly promising semiconducting materials for a wide range of optoelectronic and energy applications. Nevertheless, the rotational dynamics of the organic components and many-molecule interdependencies, which may strongly impact the functional properties of HOIP, are not yet fully understood. In this study, we quantitatively analyze the orientational disorder and molecular correlations in archetypal perovskite CH3NH3PbI3 (MAPI) by performing comprehensive molecular dynamics simulations and entropy calculations. We found that, in addition to the usual vibrational and orientational contributions, rigid molecular rotations around the C-N axis and correlations between neighboring molecules noticeably contribute to the entropy increment associated with the temperature-induced order-disorder phase transition, ΔSt. Molecular conformational changes are equally infrequent in the low-T ordered and high-T disordered phases and have a null effect on ΔSt. Conversely, the couplings between the angular and vibrational degrees of freedom are substantially reinforced in the high-T disordered phase and significantly counteract the phase-transition entropy increase resulting from other factors. Furthermore, the tendency for neighboring molecules to be orientationally ordered is markedly local, consequently inhibiting the formation of extensive polar nanodomains at both low and high temperatures. This theoretical investigation not only advances the fundamental knowledge of HOIP but also establishes physically insightful connections with contemporary technological applications like photovoltaics, solid-state cooling, and energy storage.

Core-shell gelatin-chitosan nanoparticles with lysozyme responsiveness formed via pH-drive and transglutaminase cross-linking.

Lysozyme-responsive nanoparticles were fabricated using a hydrophilic protein (gelatin type A) as the core and a hydrophobic polysaccharide (chitosan) as the shell. In this study, curcumin was used as a model molecule for encapsulation and promoted the aggregation of gelatin nanoparticles. Transglutaminase catalyzed both intra-molecular cross-linking within gelatin and inter-molecular cross-linking between gelatin and chitosan. The formation mechanism of gelatin nanoparticles was investigated by molecular docking simulations, circular dichroism spectroscopy, UV-Vis spectroscopy, turbidity analysis, and dynamic light scattering. Results indicated that pH-driven processes can induce molecular conformational changes of gelatin. However, these alone are insufficient to induce nanoparticle formation. Hydrogen bonding, Pi-alkyl interactions, Pi-Pi interactions, and van der Waals forces between gelatin and curcumin are crucial for the core formation. The coating mechanism of chitosan involved covalent bonds catalyzed by transglutaminase and electrostatic interactions, verified by dynamic light scattering and Fourier transform infrared spectroscopy. Physicochemical properties characterization revealed that the core-shell nanoparticles exhibited a maximum encapsulation efficiency of 97.2 ± 0.3 % and an average particle size of 120 ± 21 nm. The core-shell nanoparticles exhibited high thermal and pH stability, with curcumin retention rates exceeding 80 % under acidic, neutral, and weakly alkaline conditions, and detained thermal degradation up to 90 °C. Additionally, lysozyme responsiveness was evaluated by controlled curcumin release with varying lysozyme concentrations, through which enzymatic hydrolysis of chitosan by lysozyme triggered an increased release rate. In summary, core-shell nanoparticles synthesized from gelatin and chitosan may be effective target delivery systems for curcumin.

Cholesterol Conjugated Elastin-like Recombinamers: Molecular Dynamics Simulations, Conformational Changes, and Bioactivity.

Current models for elastin-like recombinamer (ELR) design struggle to predict the effects of nonprotein fused materials on polypeptide conformation and temperature-responsive properties. To address this shortage, we investigated the novel functionalization of ELRs with cholesterol (CTA). We employed GROMACS computational molecular dynamic simulations complemented with experimental evidence to validate the in silico predictions. The ELRCTA was biosynthesized and characterized by using fluorescence assays, circular dichroism, dynamic light scattering, and differential scanning calorimetry. The in silico and in vitro data showed that CTA promotes the formation of intramolecular hydrogen bonds that favor β-sheet secondary structures. Compared with an unmodified ELRVKV, CTA enhanced the hydrophobicity and stability of the system, allowing the formation of monodisperse nanoaggregates at physiologically relevant temperatures. Importantly, calorimetry assays revealed that ELRCTA interacted and intercalated with the lipid bilayers of the DPPC liposomes. To demonstrate the implications of these changes for biomedical applications, ELRCTA and DPPC-ELRCTA hybrid nanoparticles were tested with cancer and immune cell lines. Interactions with the cell membranes demonstrated a synergistic effect of the composition and size of the modified recombinamer aggregates on the internalization. The results indicated the potential use of ELR-based nanoparticles for localized and systemic drug delivery. This work sets a new precedent to design elastin-inspired biomaterials with predictable self-assembly properties and develop novel drug delivery strategies.

Exploring the application of molecular simulation technology in food sector: Focusing on food component interactions and food quality

The intricate interactions between component molecules that occur during food processing and storage are challenging to elucidate with traditional experimental techniques at the molecular level. Molecular simulation technology, conversely, offer an expedient methodology for investigating these molecular behaviors and anticipating macroscopic experimental phenomena. This review outlines the fundamental principles of molecular simulation techniques commonly employed in the field of food science and their associated computational procedures. It also examines their applications in the context of food component interactions and the quality control of proteins, carbohydrates, and lipids. This technique can be employed to elucidate the interactions between food nutrients, facilitate the rapid detection of pesticide and veterinary drug residues, identify foodborne pathogens and biotoxins, and conduct molecular mechanism analysis of toxicological effects at the atomic and molecular levels. By dynamically characterizing changes in molecular conformation, electron transfer and bonding processes, molecular simulation has become an important tool for optimizing food processing and storage conditions. Further studies should investigate the relationship between molecular conformational changes and food quality in greater depth and seek to optimize the application of molecular simulation in food science in order to provide critical insights into practical operations.

CryoSTAR: leveraging structural priors and constraints for cryo-EM heterogeneous reconstruction.

Resolving conformational heterogeneity in cryogenic electron microscopy datasets remains an important challenge in structural biology. Previous methods have often been restricted to working exclusively on volumetric densities, neglecting the potential of incorporating any preexisting structural knowledge as prior or constraints. Here we present cryoSTAR, which harnesses atomic model information as structural regularization to elucidate such heterogeneity. Our method uniquely outputs both coarse-grained models and density maps, showcasing the molecular conformational changes at different levels. Validated against four diverse experimental datasets, spanning large complexes, a membrane protein and a small single-chain protein, our results consistently demonstrate an efficient and effective solution to conformational heterogeneity with minimal human bias. By integrating atomic model insights with cryogenic electron microscopy data, cryoSTAR represents a meaningful step forward, paving the way for a deeper understanding of dynamic biological processes.

Single‐Luminophore Molecular Engineering for Rapidly Phototunable Solid‐State Luminescence

AbstractSmart materials enabling emission intensity or wavelength tuning by light stimulus have attracted attention in cutting‐edge fields. However, due to the general limitation of the dense molecular stacking (in solid states, especially in crystals) on photoresponsivity, constructing rapidly phototunable solid‐state luminescent systems remains challenging. Herein, we present a new luminophore that serves as both a photoresponsive and a luminous group with enhanced conformational freedom to attain this goal, namely, relying on photoexcitation‐induced molecular conformational change of an ionized persulfurated arene based on weak intermolecular aliphatic C−H⋅⋅⋅π interaction. Together with the phosphorescence characteristic of the molecule itself, rapidly enhanced phosphorescence upon irradiation can be observed in a series of phase states, like solution state, crystal, and amorphous state, especially with a high photoresponsive rate of 0.033 s−1 in crystal state that is superior to the relevant reported cases. Moreover, a rapidly phototunable afterglow effect is achieved by extending this molecule into some polymer‐based doping systems, endowing the system with unique dynamic imaging and fast photopatterning capabilities. This single‐luminophore molecular engineering and underlying mechanism have implications for building other condensed functional materials, principally for those with stimuli responses in solid states.

Single-Molecule adenosine detection and chiral selectivity by DNA aptamer conformational changes using α-Hemolysin nanopore

Nucleic acid aptamers, which are short single-stranded RNA or DNA molecules, undergo conformational changes upon recognizing small molecules. However, their structural characterization is challenging due to the flexibility of single-stranded oligonucleotides. Nanopores provide a sensitive method for single-molecule analysis of molecular conformational changes as they transport through the pore. In this study, we employed α-hemolysin (α-HL) nanopore with high spatiotemporal resolution to investigate the conformational changes of DNA aptamer (ADO-23) upon binding to adenosine (Ado) molecules. Unlike the events generated by the aptamer alone, the DNA-Ado complex produced two distinct new characteristic events, indicating the formation of two unique secondary structures. By analyzing current events, the structures formed by the DNA-Ado complex were speculated to be hairpin DNA and G-quadruplex (G4) DNA. Furthermore, we demonstrated the potential of the aptamer as a chiral selector within the nanopore. The results showed that the aptamer specifically bound to D-Ado and not to L-Ado. Finally, we realized specific and sensitive detection of small molecule Ado by α-HL pore, with a detection limit as low as 10.5 nM, and successfully applied it to the detection of real human serum samples. The nanopore platform provides a powerful tool for studying small molecule-biomolecule conformational changes, and we constructed sensors for detecting adenosine through the aptamer. This work also offers a promising new approach to the recognition of enantiomers at the single-molecule level.

Investigation of orientation behavior of nematic liquid crystals on UV-irradiated polyimide films

Abstract The orientation mechanism of liquid crystals (LCs) on surfaces remains unclear, despite several methods for controlling pretilt angles. This study investigates the relationship between the surface condition of polyimide films, whose pretilt angles can be controlled by UV dose, and LC orientation behavior. Absorbance at wavelength of 200 nm and 260 nm significantly decrease, while thickness reduces approximately 4 nm. A rubbing treatment further decreases the thickness by approximately 2 nm. Atomic force microscopy confirmed the change in molecular conformation by UV-irradiation and rubbing treatment. The dispersive and polar components of the surface free energy of UV-irradiated polyimide films are evaluated, it’s found that only the polar component changes with UV dose. Additionally, we confirm that the alignment of LCs transitions from homeotropic to planar with increased UV irradiation, demonstrating that pretilt angle distribution can be spatially controlled. These results contribute to establishing a photoalignment method for pretilt angle control.

Multiple Energy Transfer Modes From o‐Carborane Dyad Induced by Synergetic Conformational Regulations and Intense Circularly Polarized Luminescence in Self‐Assembly Aggregates

AbstractPhotothermal modulated excited conformations in traditional optoelectronic materials have been extensively investigated for the manipulation of emissive properties. However, photoinduced molecular synergetic conformational changes, which are promising for controlling intramolecular energy transfer modes through molecular orbital breaking, are never been explored. Herein, a novel o‐carborane dyad composed of carbazole units as electron donors and triazine derivatives as electron acceptors is demonstrated to achieve conformation‐dependent emissions and abundant emissions via synergetic conformational changes. Notably, the resulting dyad exhibited multiple conformational changes that induced emissions through different energy transfer modes involved “through space” and “through bond.” Exactly, the electron spin from singlet to triplet state took a flip accompanied by molecular orbitals from π–π molecular orbitals in the space charge transfer style to π and σ molecular orbitals in the bond charge transfer mode. The circularly polarized luminescence (CPL) properties are systematically investigated, exhibiting intense CPL with large glum values. These results provide novel perspectives for elucidating the complicated emission changes in aggregated states, as well as unique perspectives on the relationship between molecular conformations, energy transfer modes, and molecular orbital breaking.

Film-forming modifications and mechanistic studies of soybean protein isolate by glycerol plasticization and thermal denaturation: A molecular interaction perspective

Plasticizer and thermal denaturation are indeed important factors for soybean protein film formation. The objective of the study was to investigate the effects of glycerol and thermal denaturation on the film-forming performances of soybean protein isolate (SPI) and elucidate the underlying mechanisms. From the results, glycerol had almost no effect on the protein’s secondary and tertiary structures. Indeed, the dispersion of glycerol diminished the intra- or intermolecular hydrogen bonding of SPI and interacted with the amino acids of subunits through hydrogen bonding and van der Waals forces. By interfering with protein network interactions, the glycerol molecule achieved a plasticizing effect on SPI films. The effects of heat treatment on SPI film properties were mainly realized through the changes in molecular conformation caused by protein denaturation, which manifested in the enhancement of light barrier and mechanical capabilities, and markedly altered the distribution of water states within the film network. This study provided valuable insights to clarify the mechanism of protein film formation.

Photo-triggered Phase Transition of Crystals and Photoactuation.

Photo-triggered phase transition is a new type of phase transition in which a photochromic crystal with a thermal phase transition transforms into an identical high-temperature phase in a temperature region lower than the thermal phase transition temperature upon light irradiation. Here, we report a second crystal that exhibits a photo-triggered phase transition, thereby demonstrating that the photo-triggered phase transition is a general phenomenon that occurs in crystals. When the chiral salicylidenephenylethylamine crystal was irradiated with ultraviolet (UV) light, the photo-triggered phase transition occurred in the temperature range -30 to -10 °C. The photo-triggered phase transition is induced by local stress due to trans-keto molecules produced by photoisomerization near the irradiated surface. Crystal cantilevers exhibited stepwise bending by the combination of the photo-triggered phase transition and photoisomerization. Alternate irradiation with UV and visible light achieved locomotion of single crystals driven by repeated stepwise bending. Finally, a detailed comparison of photo-triggered and non-photo-triggered phase transition crystals revealed that a sufficient molecular conformation change in affordable crystal voids, smooth photoisomerization, and most likely a chiral molecular arrangement are required for inducing the photo-triggered phase transition.

Effects of cold plasma pretreatment before different drying process on the structural and functional properties of starch in Chinese yam

This article compared the effects of hot air drying (HAD), infrared drying (IRD), and cold plasma (CP) as a pretreatment on the structure, quality, and digestive characteristics of starch extracted from yam. As the most commonly used drying method, HAD was used as a control. SEM and CLSM images showed that all treatments preserve the integrity of the yam starch. CP caused some cracks and breaks in the starch granules. IRD did not destroy the crystal structure of starch molecules, but made the spiral structure tighter and increased short-range orderliness. However, CP led to the depolymerization and dispersion of starch molecular chains, resulting in a decrease in average molecular weight and relative crystallinity. These molecular conformation changes caused by different processes led to differences in solubility, swelling power, pasting parameters, digestion characteristics, and functional characteristics. This study provided an important basis for the reasonable drying preparation and utilization of yam starch.

In-tube micro-pyramidal silicon nanopore for inertial-kinetic sensing of single molecules

Electrokinetic force has been the major choice for driving the translocation of molecules through a nanopore. However, the use of this approach is limited by an uncontrollable translocation speed, resulting in non-uniform conductance signals with low conformational sensitivity, which hinders the accurate discrimination of the molecules. Here, we show the use of inertial-kinetic translocation induced by spinning an in-tube micro-pyramidal silicon nanopore fabricated using photovoltaic electrochemical etch-stop technique for biomolecular sensing. By adjusting the kinetic properties of a funnel-shaped centrifugal force field while maintaining a counter-balanced state of electrophoretic and electroosmotic effect in the nanopore, we achieved regulated translocation of proteins and obtained stable signals of long and adjustable dwell times and high conformational sensitivity. Moreover, we demonstrated instantaneous sensing and discrimination of molecular conformations and longitudinal monitoring of molecular reactions and conformation changes by wirelessly measuring characteristic features in current blockade readouts using the in-tube nanopore device.

Effects of different protein cross-linking degrees on physicochemical and subsequent thermal gelling properties of silver carp myofibrillar proteins sol subjected to freeze-thaw cycles

Knowledge regarding the denaturation process and control methods for depolymerized sol-state myofibrillar proteins (MPs) during freezing remains scant. This study investigated the effects of protein cross-linking treatment before freezing on physicochemical and subsequent gelation properties of MPs sol subjected to freeze-thaw (F-T) cycles. Results indicated that after five F-T cycles, cross-linked MPs sols showed increased high molecular weight polymers and bound water (T21a and T21b) mobility, suggesting enhanced protein-protein interactions at the expense of protein-water interactions. Upon heating after F-T cycles, gels formed from cross-linked sols exhibited significantly higher hardness, springiness, and cooking loss (P < 0.05), alongside more contracted gel networks. Correlation analysis revealed that the formation and properties of thermal gel after freezing closely relate to changes in molecular conformation and chemical bonds of cross-linked MPs sol during freezing. This study provides new insights into regulating the freezing stability and post-thawed thermal processing properties of sol-based surimi products.

An adaptive biomolecular condensation response is conserved across environmentally divergent species

Cells must sense and respond to sudden maladaptive environmental changes—stresses—to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide a remarkable view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein—a core marker of stress granules—condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.

Probing cell metabolism using the two-photon excitation autofluorescence lifetime of tryptophan.

Compared to intensity detection, fluorescence lifetime has the advantage of being unaffected by variations in excitation intensity, fluorophore concentration, or attenuation due to biological absorption and scattering. In this Letter, to the best of our knowledge, we present the use of the two-photon excitation autofluorescence lifetime imaging of tryptophan (TRP) to probe cell metabolism for the first time. Tests of pure chemical samples showed that the fluorescence lifetime of TRP was highly sensitive to changes in molecular conformation and the environment. In in vitro cell experiments, we successfully utilized the fluorescence lifetime of TRP to distinguish tumor cells from healthy cells, track the therapeutic effect of the tumor immunotherapy drug 1-MT for HeLa cells, and monitor cells in response to carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced cell apoptosis. These results reveal that the two-photon excitation autofluorescence lifetime of TRP could be a sensitive natural probe of cell metabolism in living cells.

Understanding the AIE phenomenon of nonconjugated rhodamine derivatives via aggregation-induced molecular conformation change

The bottom-up molecular science research paradigm has greatly propelled the advancement of materials science. However, some organic molecules can exhibit markedly different properties upon aggregation. Understanding the emergence of these properties and structure-property relationship has become a new research hotspot. In this work, by taking the unique closed-form rhodamines-based aggregation-induced emission (AIE) system as model compounds, we investigated their luminescent properties and the underlying mechanism deeply from a top-down viewpoint. Interestingly, the closed-form rhodamine-based AIE system did not display the expected emission behavior under high-viscosity or low-temperature conditions. Alternatively, we finally found that the molecular conformation change upon aggregation induced intramolecular charge transfer emission and played a significant role for the AIE phenomenon of these closed-form rhodamine derivatives. The application of these closed-form rhodamine-based AIE probe in food spoilage detection was also explored.

Total variation denoising-based method of identifying the states of single molecules in break junction data

Break junction (BJ) measurements provide insights into the electrical properties of diverse molecules, enabling the direct assessment of single-molecule conductances. The BJ method displays potential for use in determining the dynamics of individual molecules, single-molecule chemical reactions, and biomolecules, such as deoxyribonucleic acid and ribonucleic acid. However, conductance data obtained via single-molecule measurements may be susceptible to fluctuations due to minute structural changes within the junctions. Consequently, clearly identifying the conduction states of these molecules is challenging. This study aims to develop a method of precisely identifying conduction state traces. We propose a novel single-molecule analysis approach that employs total variation denoising (TVD) in signal processing, focusing on the integration of information technology with measured single-molecule data. We successfully applied this method to simulated conductance traces, effectively denoise the data, and elucidate multiple conduction states. The proposed method facilitates the identification of well-defined plateau lengths and supervised machine learning with enhanced accuracies. The introduced TVD-based analytical method is effective in elucidating the states within the measured single-molecule data. This approach exhibits the potential to offer novel perspectives regarding the formation of molecular junctions, conformational changes, and cleavage.