Molecular Conformational Changes Research Articles

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.

Efficient microwave-assisted synthesis of 1-hexylpyridin-1-ium bromide: Anion exchange to acetate and fundamentals tools to probe its interaction with RuCl3

The study presents a robust and efficient method for synthesizing high-purity 1-hexylpyridin-1-ium acetate (1-HP-Ac), a room-temperature ionic liquid (RTIL), using microwave synthesis. The study also explores its interaction with ruthenium trichloride (RuCl3). Initially, we employed classical solvothermal methods to obtain 1-hexypyridin-1-ium bromide (1-HP-Br), a precursor for 1-HP-Ac. Issues related to impurity and time constraints necessitated a transition to microwave-assisted synthesis, which emerged as an eco-friendly, energy-efficient approach. Microwave synthesis proved superior by delivering shorter reaction times (30 min), higher yields, and eliminating the need for solvents or inert atmospheres. Various characterization techniques (1H NMR, 13C NMR, FTIR, TGA, and HRMS) and matching quantum mechanical NMR predictions confirmed the successful synthesis of the hexylpyridinium cation and anion exchange transforming 1-HP-Br into its acetate form. The interaction between the synthesized RTIL and RuCl3 was monitored through NMR-based titrations and molecular dynamics (MD) modeling. The study explored the effects of increasing amounts of either RTIL or RuCl3 with the critical inflection point at a 1:2 ratio of 1-HP-Ac to RuCl3 for effective interactions and potential changes in average molecular conformation. Specifically, examining Karplus J-coupling constants provided information about dihedral angles within 1-HP-Ac. The data suggested that RuCl3 has a discernible influence on these angles, particularly for aliphatic protons. With thermal stability up to 200 °C, 1-HP-Ac is a fitting candidate for high-temperature reactions. MD simulation quantifies the solvation environment created by the IL as well as elucidates interactions of 1-HP-Ac with the RuCl3 crystal structure. The insights gained from our research into 1-HP-Ac's interaction with RuCl3, combined with the efficiency of microwave-assisted synthesis, open new avenues for further studies in catalysis, material science, and related fields..

Pressure-induced luminescence evolution of 3,3′-diamino-4,4′-azofurazan: Role of restricting chemical bond vibration and conformational modification

The luminescence and electronic structure of 3,3′-Diamino-4,4′-azofurazan (DAAzF) were studied under high pressure conditions through experimental and calculation approaches. The transition of π* → π was primarily responsible for DAAzF's broad light emission. Upon applying pressure to DAAzF, high-pressure-stiffened hydrogen-bond interactions enable the restriction of the stretching vibration of NH2 group. The reduced energy loss through nonradiative rotational relaxation and molecular motions lead to a ∼20 times luminescent enhancement of DAAzF from 1 atm to 8.9 GPa. With the further strengthening of interlayer hydrogen bond interactions at higher pressure, the deviation of hydrogen atoms in amino groups from the molecular plane lessens the radiation transition efficiency. In addition, the bending of the C–C–N=N bond further leads to molecular conformation changes at approximately 20.7 GPa, which induces an abrupt redshift and moderate quenching of the luminescence. Furthermore, the band gap of DAAzF is significantly influenced by pressure. As the color undergoes a transition from yellow to red, and becomes darker as the pressure increases, the absorption edge shifted towards red. At 3.4, 9, and 21 GPa, three conformational variations were identified in conjunction with electronic structural alterations.

Changes in molecular conformation and electronic structure of DNA under 12C ions based on first-principles calculations

Fundamental studies on the interaction between ionizing radiation and deoxyribonucleic acid (DNA) can contribute to understanding the biological effects of radiation protection and radiotherapy. The transitional process from ionized and excited DNA to DNA lesions, such as strand breaks and base lesions, remains uncertain. In this study, we focused in particular on the direct effects of radiation on DNA and calculated the number of ionizations induced within 10 base pairs of DNA using the Particle and Heavy Ion Transport code System, a general-purpose Monte Carlo code for radiation transport. The electronic structure of the ionized DNA is subsequently calculated using the first-principles calculation software OpenMX. Through these calculations, we successfully identified the redox site of DNA and quantitatively evaluated the amount of molecular bond cleavage. The scientific findings of this study will elucidate the cleavage mechanism of DNA in the high-density radiation field realized by ion beam irradiation by determining the redox sites.

Polarization-resolved surface-enhanced infrared spectra with nanosensors based on self-organized gold nanorods

Biosensors are becoming ubiquitous in the study of biomolecules, as, by modifying shape size and environment of metallic nanostructures it is now possible to engineer the field so to monitor subtle transient changes in molecular conformation at the level of a single biolayer. In this paper, we present a first step towards a polarization-resolved study of light-induced conformational changes of transmembrane proteins. We exploit a platform of self-organized gold nanorods on SiO2 substrates to enhance the infrared reflection absorption spectroscopy and to perform difference spectroscopy (i.e., spectrum under visible light ON minus spectrum under visible light OFF) on a light-sensitive transmembrane protein with simultaneous visible light illumination from the backside of the chip. The broad size distribution of nanorods allows us to probe with high sensitivity the modifications of the vibrational peaks over the entire fingerprint region. We show that it is possible to identify dissimilarities in the difference spectra, which in turn implies that we are monitoring over a broadband spectrum not only the chemical bonds with the dipole moment aligned orthogonally to our substrate/nanorod surface but also those with different orientation.