Chain Conformation Research Articles

Molecular parameters, conformation and rigidity of polyamic acid chains in dimethyl formamide investigated by gel permeation chromatography coupled with multiple detectors

Molecular parameters, conformation and rigidity of polyamic acid chains in dimethyl formamide investigated by gel permeation chromatography coupled with multiple detectors

Fine-Tuning Conformation of PEDOT Chains Enables Simultaneously Enhanced Conductivity, Work Function, Transmittance, and Waterproofness in PEDOT:PSS Interlayer for Highly Efficient and Stable Organic Photovoltaics.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is widely utilized as the hole transport layer (HTL) inorganic photovoltaics (OPVs) because of its low-temperature solution processing peculiarity, high optical transmittance, and excellent mechanical flexibility. However, the core-shell structure of PSS coated PEDOT results in relatively low conductivity, work function, transmittance and waterproofness of PEDOT:PSS interlayer, limiting the photovoltaic performance and stability of OPVs. Here, the conformation of PEDOT chains are regulated from helical benzoyl to linear quinone structure via incorporation of 2D Cd0.85PS3Li0.15H0.15dopant into the conventional PEDOT:PSS interlayer, promoting an interpenetrating network structure in PEDOT:PSS interlayer and forming an efficient hole transport channel from active layer to ITO electrode. Such features significantly improve the electrical conductivity, work function, and transmittance of PEDOT:PSS interlayer. In consequence, the maximum power conversion efficiency (PCE) of D18:L8-BO, PBDB-T:ITIC, as well as PTzBI-dF:L8-BO based OPVs ameliorated from 18.37%, 8.94%, and 15.80% to 19.26%, 10.00%, and 16.83%, respectively. The application of Cd0.85PS3Li0.15H0.15 doping PEDOT:PSS strategy demonstrates great potential for the development of strongly conductive, large-work-function, highly transparent, and excellent-waterproof PEDOT:PSS interlayer toward highly efficient and stable OPVs.

Chain Conformation of Polymers Densely Grafted onto Plate-Shaped Particles

Chain Conformation of Polymers Densely Grafted onto Plate-Shaped Particles

Dynamics of Polymer Chains in Disperse Melts: Insights from Coarse-Grained Molecular Dynamics Simulations.

Synthetic polymers have a distribution of chain lengths which can be characterized by dispersity, Đ. Their macroscopic properties are influenced by chain mobility in the melt, and controlling Đ can significantly impact these properties. In this work, we present a detailed study of the static and dynamic behavior of fully flexible polymer chains that follow the Schulz-Zimm molecular weight distribution up to Đ = 2.0 using coarse-grained molecular dynamics simulations. We analyze the behavior of test chains with molecular weights that are equal to, above, or below the molecular weight (Mw) of the melt. Static analysis shows that the conformation of these test chains remains unaffected by the heterogeneity of the surrounding chains. To study the dynamics, we computed the mean-squared displacement of test chains in melts of the same Mw and different dispersities. The mobility of test chains with N > Mw steadily increases with dispersity, due to the shorter chains contributing to early onset of disentanglement of the long chains. However, the dynamics of test chains of length N < Mw is nonmonotonic with respect to dispersity; this behavior arises from a trade-off between the increased mobility of shorter chains and the corresponding slowdown caused by the presence of longer chains. We examine the dynamic structure factor and find a weakening of tube confinement, with the effects becoming less pronounced with increasing dispersity and Mw. These findings provide insights into the rich dynamic heterogeneity of disperse polymer melts.

Quantitative Examination and Mechanistic Insights of Polymer Chain Conformation Confined in Nanopores by Time-Resolved Fluorescence Resonance Energy Transfer.

The conformational studies of polymers confined at the nanoscale remain challenging and controversial due to the limitations of characterization techniques. In this study, we utilized the high sensitivity of time-resolved fluorescence resonance energy transfer (trFRET) and a site-specific dye-labeling strategy to characterize the conformation of polymer chains confined in anodic aluminum oxide (AAO) nanopores. This strategy introduced a fluorescent donor (carbazole) and acceptor (anthracene) at the center of poly(butyl methacrylate) (PBMA) chains grown by atom transfer radical polymerization (ATRP). By quantitatively analyzing fluorescence decay through the Förster mechanism and the Drake-Klafter-Levitz (DKL) formalism, we can determine both the energy transfer efficiency and the spatial distribution of the dyes. This analysis revealed that the PBMA chains, with a molecular weight of 40 kDa, maintained their bulk-like conformation even when confined within nanopores as small as 10 nm in diameter. This study is the first to demonstrate the use of trFRET for investigating chain conformation in confined polymer systems, which can be generalized to other polymer types and polymer topologies in different confined geometries.

Solvent induced crystallization and phase transition of syndiotactic polymethoxystyrene investigated using In situ wide angle X-ray diffraction

Solvent induced crystallization and phase transition is an interesting phenomenon that has been observed in many kinds of semicrystalline polymer. In the case of syndiotactic polystyrene (SPS) which exhibits complicated phase transition behavior, this process may be different when the phenyl rings are substituted by polarity groups. In our previous work, the crystal structures of a series of –OCH3 (OMe) substituted SPS and OMe-SPS/solvent complexes were analyzed (Macromolecules2021, 54, 1881 and Macromolecules2022, 55, 8222). In this particular work, the phase transition behavior of OMe-SPS, especially meta-OMe-SPS with different initial crystalline structures was discussed based on in situ 2-dimensional wide-angle X-ray diffractions (2D-WAXD) in the presence of organic solvent. It is found that meta-OMe-SPS in amorphous state and mesophase shows similar solvent induced phase transition like the cases of SPS. Meanwhile, highly crystalline and oriented meta-OMe-SPS also exhibits organic solvent induced phase transition from β form with planar zigzag conformation into δ form with helical conformation, which has not been observed in SPS. The subsequent heating of meta-OMe-SPS δ and γ forms does not form β form, which is also unlike the situation of SPS δ/δe-γ-α/β transition. The OMe substituted group that changes the polarity of the phenyl rings may be the chemical structure region of affecting the chain conformation energy and phase transition behavior.

All‐Atom Protein Sequence Design Based on Geometric Deep Learning

AbstractDesigning sequences for specific protein backbones is a key step in creating new functional proteins. Here, we introduce GeoSeqBuilder, a deep learning framework that integrates protein sequence generation with side chain conformation prediction to produce the complete all‐atom structures for designed sequences. GeoSeqBuilder uses spatial geometric features from protein backbones and explicitly includes three‐body interactions of neighboring residues. GeoSeqBuilder achieves native residue type recovery rate of 51.6 %, comparable to ProteinMPNN and other leading methods, while accurately predicting side chain conformations. We first used GeoSeqBuilder to design sequences for thioredoxin and a hallucinated three‐helical bundle protein. All the 15 tested sequences expressed as soluble monomeric proteins with high thermal stability, and the 2 high‐resolution crystal structures solved closely match the designed models. The generated protein sequences exhibit low similarity (minimum 23 %) to the original sequences, with significantly altered hydrophobic cores. We further redesigned the hydrophobic core of glutathione peroxidase 4, and 3 of the 5 designs showed improved enzyme activity. Although further testing is needed, the high experimental success rate in our testing demonstrates that GeoSeqBuilder is a powerful tool for designing novel sequences for predefined protein structures with atomic details. GeoSeqBuilder is available at https://github.com/PKUliujl/GeoSeqBuilder.

Multiscale Analyses of Strain-Enhanced Charge Transport in Conjugated Polymers.

The advancement of flexible and wearable electronics relies on semiconducting polymers that can endure mechanical deformation while maintaining high electrical performance under strain. In this study, we demonstrate that fine-tuning backbone rigidity through the molecular design of donor moieties significantly enhances both the mechanical and charge transport properties of diketopyrrolopyrrole (DPP)-based polymers. Specifically, the flexible DPP-4T (quaterthiophene) exhibited a persistence length of 20.4 nm in solution, while DPP-DTT (dithienothiophene) showed a longer persistence length of 32.8 nm due to its stiff backbone, as confirmed by small-angle neutron scattering and Monte Carlo simulations. This flexibility enabled DPP-4T to achieve a crack-onset strain exceeding 100% via the film-on-elastomer method and a fracture strain of over 30% in quasi-free-standing films. Additionally, DPP-4T demonstrated a 180% increase in hole mobility at 80% strain, driven by strain-induced chain alignment and backbone planarization. Utilizing a range of characterization techniques, including ultraviolet-visible (UV-vis) spectroscopy, grazing incidence X-ray diffraction (XRD), and Raman spectroscopy, we characterized structural changes at multiple length scales under applied tensile strain. Notably, strain induced a transformation in chain conformation from a twisted to a flat structure, reducing the hopping energy barrier and enhancing charge transport. These structural rearrangements are crucial for sustaining efficient charge transport and ensuring the reliability of electronic performance under mechanical stress.

Molecular dynamics simulation: Effect of sulfation on the structure of curdlan triple helix in aqueous solution

In this work, by using molecular dynamics simulations, we elucidate the effect of sulfation substitution on the stability of the curdlan triple helix structure. The simulation results indicate that the stability of the triple helix structure is significantly influenced by the sites of sulfation substitution. The substitution at the O2 site directly disrupts the hydrogen bonding network between the triple helix chains, significantly destroying the triple helix conformation. When substitutions occur at both the O4 and O6 sites simultaneously (O4,6), the electrostatic repulsion between numerous sulfate groups introduces considerable energy perturbation to the triple helix, leading to alterations in the glucan chain conformation and consequent destabilization of the triple helix structure. Meanwhile, we find that even if the sulfation substitution is performed at the same substitution sites, the difference in the degree of substitution also has an impact on the triple helix stability. The resistance of the triple helix to sulfation substitution at O2 is weak, and low degree of substitution can lead to the unwinding of the triple helix. However, it demonstrates higher resistance to substitution at O4,6 where only higher degree of substitution results in triple helix destabilization.

All-Atom Protein Sequence Design Based on Geometric Deep Learning.

Designing sequences for specific protein backbones is a key step in creating new functional proteins. Here, we introduce GeoSeqBuilder, a deep learning framework that integrates protein sequence generation with side chain conformation prediction to produce the complete all-atom structures for designed sequences. GeoSeqBuilder uses spatial geometric features from protein backbones and explicitly includes three-body interactions of neighboring residues. GeoSeqBuilder achieves native residue type recovery rate of 51.6 %, comparable to ProteinMPNN and other leading methods, while accurately predicting side chain conformations. We first used GeoSeqBuilder to design sequences for thioredoxin and a hallucinated three-helical bundle protein. All the 15 tested sequences expressed as soluble monomeric proteins with high thermal stability, and the 2 high-resolution crystal structures solved closely match the designed models. The generated protein sequences exhibit low similarity (minimum 23 %) to the original sequences, with significantly altered hydrophobic cores. We further redesigned the hydrophobic core of glutathione peroxidase 4, and 3 of the 5 designs showed improved enzyme activity. Although further testing is needed, the high experimental success rate in our testing demonstrates that GeoSeqBuilder is a powerful tool for designing novel sequences for predefined protein structures with atomic details. GeoSeqBuilder is available at https://github.com/PKUliujl/GeoSeqBuilder.

Molecular Modeling of Glycosylated Catalytic Domain of Human Carbonic Anhydrase IX.

Glycans exhibit significant structural diversity due to the flexibility of glycosidic bonds linking their constituent monosaccharides and the formation of numerous hydrogen bonds. The present work searches a simulated ensemble of glycan chain conformations attached to the catalytic domain of N-glycosylated human carbonic anhydrase IX (HCA IX-c) to identify conformations pointed away or back-folded toward the protein surface guided by different amino acid residues. A series of classical molecular dynamics (MD) simulation studies for a total of 30 μs followed by accelerated MD simulations for a total of 2 μs have been performed using two different force fields to capture varying degrees of fluctuations of both glycan chain and HCA IX. From the underlying free energy profile and kinetics derived using hidden Markov state model, several stable glycan orientations are identified that extend away from the protein surface and convert among each other with rate constants of the order 107-1010 S-1. Most importantly, we have identified a rare glycan conformation which reaches close to a catalytically important amino acid residue, Glu-106. We further enlist the protein residues that couple such less frequent event of the glycan chain back-folding toward the surface of the protein.

The synergistic enhancement or inhibition of different molecular weight components of mannoproteins after ultrafiltration on the encapsulation.

This study investigated the effects of molecular weight regulation on mannoproteins (MPs) in encapsulating both monomeric and oligomeric proanthocyanidins (MOPC). To achieve this, two different conformations of MPs were fractionated by ultrafiltration into two main molecular weight components. The results indicated that regulating molecular weight through ultrafiltration altered the conformation of MPs chains, which in turn affected the intermolecular forces with MOPC. Specifically, the interactions among the different molecular weight components of MPs formed a cross-linking network. High molecular weight components provided external support to this network, while low molecular weight components contributed to internal stabilization. The dense, flexible, and irregular coil structure of MPs facilitated the entry of MOPC into the internal spaces of the cross-linking network. Additionally, protein unfolding into a more stable β-sheet structure further stabilized MPs' cross-linking network, enhancing its capacity to encapsulate MOPC. The presence of more hydrophobic regions and positive charges within the proteins increased the number of binding sites for MOPC. This study aimed to identify the primary structural forms of MPs with potent initial bitter inhibition capabilities on MOPC, and a proposed ultrafiltration method was introduced to modify the triple helix structure of polysaccharide, offering a foundational theoretical framework for enhancing the functional attributes of current or prospective MPs. Additionally, the mixed regulation of polysaccharides with varying conformations was also beneficial for guiding the production of high-efficiency polysaccharide products.

The Structure Characterization of Polysaccharides from Codonopsis pilosula and the Structure-activity Relationship with Immune-regulation on THP-1 Cells.

In recent years, polysaccharides from Codonopsis pilosula (CPs) have received increasing attention for their excellent behaviors in immune-regulation. However, the relationship between the structure and immunomodulatory activity has rarely been reported. In this work, four fractions purified from crude CPs (CPW, CPS0.2, CPS0.5, CPS1) by chromatographic column separation were explored with both structure and immunomodulatory effects by THP-1 cells. The results showed that the monosaccharide composition, chain conformation, molecular weight (Mw) and aggregated state of CPs were different. At the same time, the immunomodulatory effects of CPs were also varied depend on structure differences, as indicated by the released cytokines of TNF-α and IL-1β by LPS-induced THP-1 cells. Finally, we summarized and concluded that the spherical structure and smaller particle size of CPs were the key factors attributed to better immune-enhancing effects. The results showed that the monosaccharide combination differences of polysaccharides might lead to anti-inflammatory or pro-inflammatory activity. Moreover, the higher percentage of glucose, the relatively large particle size, as well as the extended chain conformation of CPs might be the key factors attributed to better immune-enhancing effects. This study aims to provide a theoretical basis for establishing the structure-activity relationship of CPs.

A foundational framework for the mesoscale modeling of dynamic elastomers and gels

Discrete mesoscale network models, in which explicitly modeled polymer chains are replaced by implicit pairwise potentials, are capable of predicting the macroscale mechanical response of polymeric materials such as elastomers and gels, while offering greater insight into microstructural phenomena than constitutive theory or macroscale experiments alone. However, whether such mesoscale models accurately represent the molecular structures of polymer networks requires investigation during their development, particularly in the case of dynamic polymers that restructure in time. We here introduce and compare the topological and mechanical predictions of an idealized, reduced-order mesoscale approach in which only tethered dynamic bonding sites and crosslinks in a polymer’s backbone are explicitly modeled, to those of molecular theory and a Kremer–Grest, coarse-grained molecular dynamics approach. We find that for short chain networks (∼12 Kuhn lengths per chain segment) at intermediate polymer packing fractions, undergoing relatively slow loading rates (compared to the monomer diffusion rate), the mesoscale approach reasonably reproduces the chain conformations, bond kinetic rates, and ensemble stress responses predicted by molecular theory and the bead–spring model. Further, it does so with a 90% reduction in computational cost. These savings grant the mesoscale model access to larger spatiotemporal domains than conventional molecular dynamics, enabling simulation of large deformations as well as durations approaching experimental timescales (e.g., those utilized in dynamic mechanical analysis). While the model investigated is for monodisperse polymer networks in theta-solvent, without entanglement, charge interactions, long-range dynamic bond interactions, or other confounding physical effects, this work highlights the utility of these models and lays a foundational groundwork for the incorporation of such phenomena moving forward.

Evolution of [formula omitted]-spacing in clay with PEG bulk volume fraction and molecular weight: Theoretical and experimental study

In the pursuit of ensuring the sustainability of the construction sector and fortifying its resilience against climate change, scientists have dedicated significant efforts to explore new classes of innovative, affordable, and technologically advanced materials that exhibit high efficiency, thereby securing the future for generations to come. In this context, we have opted to produce clay-polymer ecosystems through the direct insertion process. The PEG2000/clay and PEG6000/clay composites underwent analysis using X-ray diffraction (XRD) techniques, revealing the evolution of dhklconcerning the PEG bulk volume fraction. The results indicate the presence of two adsorption cycles, each comprising three stages (dilute, two-dimensional semi-dilute, and plateau). Each cycle delineates the incorporation of a polymer layer into the interlayer spaces of clay minerals. To elucidate this adsorption process, we have proposed a model depicting PEG chain conformation in confined spaces, represented as both monolayer and bilayer configurations. The influence of PEG molecular weight is distinctly evident in the dhklevolution across various clay categories. Ultimately, the application of scaling theory to model the experimental results proves to be robust, offering a precise description of the three discussed regimes.

Integrating 19F Distance Restraints for Accurate Protein Structure Determination by Magic Angle Spinning NMR Spectroscopy.

Traditional protein structure determination by magic angle spinning (MAS) solid-state NMR spectroscopy primarily relies on interatomic distances up to 8 Å, extracted from 13C-, 15N-, and 1H-based dipolar-based correlation experiments. Here, we show that 19F fast (60 kHz) MAS NMR spectroscopy can supply additional, longer distances. Using 4F-Trp,U-13C,15N crystalline Oscillatoria agardhii agglutinin (OAA), we demonstrate that judiciously designed 2D and 3D 19F-based dipolar correlation experiments such as (H)CF, (H)CHF, and FF can yield interatomic distances in the 8-16 Å range. Incorporation of fluorine-based restraints into structure calculation improved the precision of Trp side chain conformations as well as regions in the protein around the fluorine containing residues, with notable improvements observed for residues in proximity to the Trp pairs (W10/W17 and W77/W84) in the carbohydrate-binding loops, which lacked sufficient long-range 13C-13C distance restraints. Our work highlights the use of fluorine and 19F fast MAS NMR spectroscopy as a powerful structural biology tool.

Discovery of Bis-imidazolecarboxamide Derivatives as Novel, Potent, and Selective TNIK Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis.

Traf2- and Nck-interacting kinase (TNIK) has been identified as a promising therapeutic target for the treatment of fibrosis-driven diseases. Utilizing a structure-based drug design workflow, we developed a series of potent TNIK inhibitors that modulate the conformation of the gatekeeper Met105 side chain and access the TNIK back pocket. The lead optimization efforts culminated in the discovery of the recently reported compound 4 (INS018_055), a novel TNIK inhibitor. This molecule demonstrated excellent activity in both enzymatic and cell-based assays, along with high selectivity in a kinome panel. Further, in vitro and in vivo preclinical studies revealed favorable in vitro and in vivo DMPK properties. Results from multiple cell-based and animal models proved that compound 4 exhibits considerable antifibrotic and anti-inflammatory efficacy. Currently, phase II clinical trials of compound 4 are underway for the treatment of idiopathic pulmonary fibrosis (IPF).

Potent and Protease Resistant Azapeptide Agonists of the GLP‐1 and GIP Receptors

AbstractThe gut‐derived peptide hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) play important physiological roles including glucose homeostasis and appetite suppression. Stabilized agonists of the GLP‐1 receptor (GLP‐1R) and dual agonists of GLP‐1R and GIP receptor (GIPR) for the management of type 2 diabetes and obesity have generated widespread enthusiasm and have become blockbuster drugs. These therapeutics are refractory to the action of dipeptidyl peptidase‐4 (DPP4), that catalyzes rapid removal of the two N‐terminal residues of the native peptides, in turn severely diminishing their activity profiles. Here we report that a single atom change from carbon to nitrogen in the backbone of the entire peptide makes them refractory to DPP4 action while still retaining full potency and efficacy at their respective receptors. This was accomplished by use of aza‐amino acids, that are bioisosteric replacements for α‐amino acids that perturb the structural backbone and local side chain conformations. Molecular dynamics simulations reveal that aza‐amino acid can populate the same conformational space that GLP‐1 adopts when bound to the GLP‐1R. The insertion of an aza‐amino acid at the second position from the N‐terminus in semaglutide and in a dual agonist of GLP‐1R and GIPR further demonstrates its capability as a viable alternative to current DPP4 resistance strategies while offering additional structural variation that may influence downstream signaling.

A polysaccharide with a triple helix structure from Agaricus bisporus: Characterization and anti-colon cancer activity

In this study, A polysaccharide WAAP-2 (121 kDa) with a triple-helical structure was isolated and purified from Agaricus bisporus for the first time. The physicochemical properties, structural characteristics and anti-colon cancer activity were preliminarily investigated. The primary structure indicated that WAAP-2 was composed of mannose, glucose and galactose and determined the position of the linkage between monosaccharide residues. The advanced structure revealed that WAAP-2 has a triple helix and tangled chain conformation. In the anti-colon cancer activity investigation, WAAP-2 exerted an apoptosis-inducing effect by causing HT-29 cell cycle arrest in S phase. WAAP-2 promoted HT-29 cell apoptosis by up-regulating the expression of Caspase-3 and Bax proteins while down-regulating the expression of Bcl-2 protein. Besides, WAAP-2 could inhibit the migration and invasion of colorectal cancer cells by inducing E-cadherin expression and inhibiting Vimentin expression to affect epithelial mesenchymal transition. This paper is of importance for the application of WAAP-2, a triple-helical structural polysaccharide from Agaricus bisporus, to low-toxicity anti-colon cancer drugs.

Influence of functional group structures in nucleating agents on the crystallization behavior of poly(ethylene terephthalate)

AbstractNucleating agents are crucial for modifying semi‐crystalline polymers, but the impact of different end‐group structures on crystallization behavior remains unclear. This study synthesized succinic dihydrazide nucleating agents with various end groups (methyl, ethyl, and tert‐butyl) for PET composite materials. The tert‐butyl‐terminated nucleating agent showed the best performance, increasing the crystallization peak temperature to 203.8°C, crystallinity to 27.3%, and reducing half‐crystallization time to 2.8 min at 220°C. It also enhanced the impact strength to 47.2 kJ·m−2 and flexural modulus to 2623 MPa, while improving Vicat softening temperature and heat distortion temperature by 41 and 8°C, respectively. The results from FTIR and Raman Spectroscopy indicate that the interactions between the end groups of the nucleating agent and the CH bonds in the PET structure, the π–π interactions between the nucleating agent and the PET molecular structure, as well as the modulation of the PET chain conformation by the nucleating agent, are the primary factors contributing to the enhanced crystallinity of PET. This study provides a new approach for designing efficient nucleating agents for high‐performance materials.