Molecular Behavior Research Articles

EMA beamline at Sirius: A versatile platform to probe glass and glass ceramics under extreme thermodynamic conditions

AbstractGlass and glass ceramics are very functional materials, albeit their structural complexity. Their relevance ranges from fundamental science problems in the fields of physics, chemistry, and geoscience, to applications in health areas, engineering, or technological matters that require high performance. Enhancing our understanding of these materials' performance and refining sample preparation methods remains paramount in this field. Synchrotron facilities offer a suite of powerful techniques for the detailed characterization of glasses and glass ceramics. These methods provide valuable insights into their atomic and molecular structure, phase transformations, mechanical behavior, and thermal properties, ultimately contributing to the development of improved materials for a wide range of applications. In‐depth investigations conducted under extreme conditions of pressure and temperature have yielded pivotal insights into densification mechanisms, phase transitions, crystallization kinetics, and their consequential macroscopic properties. The emergence of fourth‐generation synchrotrons brings in a wave of novel experimental possibilities that may exert a profound influence on this field in the coming decade. In this study, we unveil a selection of the remarkable capabilities now accessible to researchers at the Brazilian Synchrotron Light Source—Sirius, within the realm of extreme methods of analysis (EMA) beamline for investigating vitreous systems under extreme conditions.

THEORETICAL DESCRIPTION OF PUCKER STATES OF CYCLIC GROUPS OF CAROTENOIDS

Carotenoids are one of the largest classes among biological pigments. They are found both in free form (dissolved in hydrophobic environments), and bound in stoichiometric complexes with protein (carotenoproteins). The interaction between the carotenoid and the protein environment is determined by the molecular conformation and dynamic behavior of the cofactor. In this work, using molecular modeling methods, we analyzed the entire set of alternative conformational states of cyclic carotenoids. The result of the theoretical study is an energysorted catalog of alternative conformational states for biogenic cyclic carotenoids and their optical isomers. The conformational states characterized in this study can be used to correctly select initial conditions when solving problems of molecular modeling of carotenoproteins

THEORETICAL DESCRIPTION OF PUCKER STATES OF CYCLIC GROUPS OF CAROTENOIDS

Carotenoids are one of the largest classes among biological pigments. They are found both in free form (dissolved in hydrophobic environments), and bound in stoichiometric complexes with protein (carotenoproteins). The interaction between the carotenoid and the protein environment is determined by the molecular conformation and dynamic behavior of the cofactor. In this work, using molecular modeling methods, we analyzed the entire set of alternative conformational states of cyclic carotenoids. The result of the theoretical study is an energysorted catalog of alternative conformational states for biogenic cyclic carotenoids and their optical isomers. The conformational states characterized in this study can be used to correctly select initial conditions when solving problems of molecular modeling of carotenoproteins

From Bulk to Single Molecules: Surface-Enhanced Raman Scattering of Cytochrome C Using Plasmonic DNA Origami Nanoantennas.

Cytochrome C, an evolutionarily conserved protein, plays pivotal roles in cellular respiration and apoptosis. Understanding its molecular intricacies is essential for both academic inquiry and potential biomedical applications. This study introduces an advanced single-molecule surface-enhanced Raman scattering (SM-SERS) system based on DNA origami nanoantennas (DONAs), optimized to provide unparalleled insights into protein structure and interactions. Our system effectively detects shifts in the Amide III band, thereby elucidating protein dynamics and conformational changes. Additionally, the system permits concurrent observations of oxidation processes and Amide bands, offering an integrated view of protein structural and chemical modifications. Notably, our approach diverges from traditional SM-SERS techniques by de-emphasizing resonance conditions for SERS excitation, aiming to mitigate challenges like peak oversaturation. Our findings underscore the capability of our DONAs to illuminate single-molecule behaviors, even within aggregate systems, providing clarity on molecular interactions and behaviors.

Shedding Light on Dark Chemical Matter: The Discovery of a SARS-CoV-2 Mpro Main Protease Inhibitor through Intensive Virtual Screening and In Vitro Evaluation.

The development of specific antiviral therapies targeting SARS-CoV-2 remains fundamental because of the continued high incidence of COVID-19 and limited accessibility to antivirals in some countries. In this context, dark chemical matter (DCM), a set of drug-like compounds with outstanding selectivity profiles that have never shown bioactivity despite being extensively assayed, appears to be an excellent starting point for drug development. Accordingly, in this study, we performed a high-throughput screening to identify inhibitors of the SARS-CoV-2 main protease (Mpro) using DCM compounds as ligands. Multiple receptors and two different docking scoring functions were employed to identify the best molecular docking poses. The selected structures were subjected to extensive conventional and Gaussian accelerated molecular dynamics. From the results, four compounds with the best molecular behavior and binding energy were selected for experimental testing, one of which presented inhibitory activity with a Ki value of 48 ± 5 μM. Through virtual screening, we identified a significant starting point for drug development, shedding new light on DCM compounds.

Research Progress of Molecular Simulation in Acrylamide Polymers with High Degree of Polymerization.

Acrylamide polymers with a high degree of polymerization are widely used in petroleum production. It is of great significance to study the oil displacement mechanism of acrylamide polymers with a high degree of polymerization from the micro level. In recent years, the rapid development of computer molecular simulation technology has filed the gaps in macroscopic experiments and theories. This technology has been highly valued in the study of the molecular behaviour of polymer systems. In this paper, the research progress of molecular simulation applied to high-polymerization-degree acrylamide polymer is summarized. The application status of acrylamide polymer flooding, the analysis of polymer flooding mechanisms, and the research progress of molecular simulation in acrylamide linear and crosslinked polymers are expounded. Finally, the development prospect of acrylamide polymer research is given, and suggestions are put forward in terms of simulation direction and simulation tools.

Molecular Weight-Dependent Physiochemical Behaviors of Calcium Carbonate Chains.

The regulation of physiochemical behaviors by changing molecular weights is an important cornerstone of polymer physics. However, similar correlations between molecular weights and properties have not been discovered in inorganic ionic compounds. In this work, we prepared a calcium carbonate specimen with a semiflexible chain topology analogous to those of polymers. The molecular weights of the calcium carbonate chains, which ranged from 3400 to 54 100 Da, were directly correlated to their physiochemical behaviors, including gel point, zero shear viscosity, and plateau modulus. The calcium carbonate chains showed similar polymeric characteristics, including shear thinning, thixotropy, entropic elasticity, and viscoelasticity. These features agreed with recent theories and formulas in polymer physics textbooks. On the basis of this understanding, the mechanical properties of calcium carbonate-based gels could be altered by changing their molecular weights. This study could represent a fusion of inorganic chemistry and polymer physics with similar molecular weight-dependent behaviors and material properties, establishing an alternative pathway for designing future inorganic materials.

A python based algorithmic approach to optimize sulfonamide drugs via mathematical modeling

This article explores the structural properties of eleven distinct chemical graphs that represent sulfonamide drugs using topological indices by developing python algorithm. To find significant relationships between the topological characteristics of these networks and the characteristics of the associated sulfonamide drugs. We use quantitative structure-property relationship (QSPR) approaches. In order to model and forecast these correlations and provide insights into the structure-activity relationships that are essential for drug design and optimization, linear regression is a vital tool. A thorough framework for comprehending the molecular characteristics and behavior of sulfonamide drugs is provided by the combination of topological indices, graph theory and statistical models which advances the field of pharmaceutical research and development.

Generation of Tailored Extracellular Matrix Hydrogels for the Study of In Vitro Folliculogenesis in Response to Matrisome-Dependent Biochemical Cues.

While ovarian tissue cryopreservation (OTC) is an important fertility preservation option, it has its limitations. Improving OTC and ovarian tissue transplantation (OTT) must include extending the function of reimplanted tissue by reducing the extensive activation of primordial follicles (PMFs) and eliminating the risk of reimplanting malignant cells. To develop a more effective OTT, we must understand the effects of the ovarian microenvironment on folliculogenesis. Here, we describe a method for producing decellularized extracellular matrix (dECM) hydrogels that reflect the protein composition of the ovary. These ovarian dECM hydrogels were engineered to assess the effects of ECM on in vitro follicle growth, and we developed a novel method for selectively removing proteins of interest from dECM hydrogels. Finally, we validated the depletion of these proteins and successfully cultured murine follicles encapsulated in the compartment-specific ovarian dECM hydrogels and these same hydrogels depleted of EMILIN1. These are the first, optically clear, tailored tissue-specific hydrogels that support follicle survival and growth comparable to the "gold standard" alginate hydrogels. Furthermore, depleted hydrogels can serve as a novel tool for many tissue types to evaluate the impact of specific ECM proteins on cellular and molecular behavior.

Effects of polyvinylpyrrolidone on the crystallization of amorphous griseofulvin: fracture and molecular mobility

This study aims to investigate the fracture, molecular mobility and crystallization behaviors of amorphous griseofulvin (GSF) in the presence of polyvinylpyrrolidone (PVP). In the presence of 10%(w/w) PVP K90, the fracture resistance of griseofulvin was greatly improved. Compared with the pure GSF system, the average fracture temperature of the griseofulvin–PVP K90 system was decreased to approximately −6.1°C. More importantly, a statistical study revealed that the direct connection between fracture and nucleation of griseofulvin was weakened in the presence of PVP K90. This study also explored the effects of PVP K90 on the molecular dynamics and crystallization behaviors of amorphous GSF. In the presence of PVP K90, the crystal growth kinetics and molecular dynamics were both slowed down. Interestingly, needle-like crystal growth was observed, exhibiting approximately the same rates as the bubble-induced process. These findings are important for understanding the complex mechanisms of physical stability of polymer-based amorphous solid dispersions.

X-LoRA: Mixture of low-rank adapter experts, a flexible framework for large language models with applications in protein mechanics and molecular design

We report a mixture of expert strategy to create fine-tuned large language models using a deep layer-wise token-level approach based on low-rank adaptation (LoRA). Starting with a set of pre-trained LoRA adapters, our gating strategy uses the hidden states to dynamically mix adapted layers, allowing the resulting X-LoRA model to draw upon different capabilities and create never-before-used deep layer-wise combinations to solve tasks. The design is inspired by the biological principles of universality and diversity, where neural network building blocks are reused in different hierarchical manifestations. Hence, the X-LoRA model can be easily implemented for any existing large language model without a need for modifications of the underlying structure. We develop a tailored X-LoRA model that offers scientific capabilities, including forward/inverse analysis tasks and enhanced reasoning capability, focused on biomaterial analysis, protein mechanics, and design. The impact of this work includes access to readily expandable and adaptable models with strong domain knowledge and the capability to integrate across areas of knowledge. Featuring experts in biology, mathematics, reasoning, bio-inspired materials, mechanics and materials, chemistry, protein biophysics, mechanics, and quantum-mechanics based molecular properties, we conduct a series of physics-focused case studies. We examine knowledge recall, protein mechanics forward/inverse tasks, protein design, adversarial agentic modeling including ontological knowledge graph construction, and molecular design. The model is capable not only of making quantitative predictions of nanomechanical properties of proteins or quantum mechanical molecular properties but also reasoning over the results and correctly predicting likely mechanisms that explain distinct molecular behaviors.

Characterization of IMIC, an implantable needle-shaped positron sensitive monolithic active pixel sensor for preclinical molecular neuroimaging

The correlation of molecular neuroimaging and behavior studies in preclinical PET imaging is of major interest to unlock progress in the understanding of brain processes and assess the validity of preclinical studies in drug development. However, fully achieving this ambition requires performing molecular images of awake and freely moving animals, whereas most of the preclinical imaging procedures are currently performed under anesthesia. To overcome this issue, the MAPSSIC project aims to develop a pixelated intracerebral probe to be implanted into awake and freely moving rats. The aforementioned probe relies on IMIC (Imageur Moléculaire Intra Cérébral), a Monolithic Active Pixel Sensor (MAPS) prototype set to directly detect positrons. The IMIC sensors were produced in 5 different configurations. Measurements using a 204Tl source showed that the sensor parameters can be optimized to boost its performance allowing to increase the sensitivity and reduce the average cluster size. In addition, comparisons between sensor configurations show a clear gain provided by the introduction of CMOS process modifications. Finally, the choice of the optimal sensor configuration will depend on the expected in vivo conditions.

Photo-Physical Characteristics of Janus Green B in Different Solvents and its Interaction Mechanism with Silver Nanoparticles.

This work explores the effects of solvent polarity on Janus Green B (JGB) photophysical properties. The Lippert-Mataga, Billot, and Ravi equations were utilized to calculate the singlet-state excited dipole moments (µe) and ground state dipole moments (µg) using absorption and fluorescence spectra analyses. The results showed an increase in the former, which is suggestive of electronic structural alterations upon excitation. Analysis of fluorescence quantum yield values revealed that JGB's environment had an impact on its emission characteristics; it was particularly sensitive to silver nanoparticles, suggesting possible interactions. While simulations of electron density, electrostatic potential, and energy gap (Eg) helped to understand the electronic structure of JGB, theoretical absorption spectra produced by Time Dependent Density Function Theory (TD-DFT) calculations offered insights into electronic transitions during absorption. To sum up, the present study contributes to our comprehension of the molecular behavior of JGB in various solvents by elucidating the intricate relationship among solvent polarity, molecular environment, and interactions with silver nanoparticles. Additionally, theoretical computations support the interpretation of experimental results.

Tripartite Motif-Containing 2, a Glutamine Metabolism-Associated Protein, Predicts Poor Patient Outcome in Triple-Negative Breast Cancer Treated with Chemotherapy.

Breast cancer (BC) remains heterogeneous in terms of prognosis and response to treatment. Metabolic reprogramming is a critical part of oncogenesis and a potential therapeutic target. Glutaminase (GLS), which generates glutamate from glutamine, plays a role in triple-negative breast cancer (TNBC). However, targeting GLS directly may be difficult, as it is essential for normal cell function. This study aimed to determine potential targets in BC associated with glutamine metabolism and evaluate their prognostic value in BC. The iNET model was used to identify genes in BC that are associated with GLS using RNA-sequencing data. The prognostic significance of tripartite motif-containing 2 (TRIM2) mRNA was assessed in BC transcriptomic data (n = 16,575), and TRIM2 protein expression was evaluated using immunohistochemistry (n = 749) in patients with early-stage invasive breast cancer with long-term follow-up. The associations between TRIM2 expression and clinicopathological features and patient outcomes were evaluated. Pathway analysis identified TRIM2 expression as an important gene co-expressed with high GLS expression in BC. High TRIM2 mRNA and TRIM2 protein expression were associated with TNBC (p < 0.01). TRIM2 was a predictor of poor distant metastasis-free survival (DMFS) in TNBC (p < 0.01), and this was independent of established prognostic factors (p < 0.05), particularly in those who received chemotherapy (p < 0.05). In addition, TRIM2 was a predictor of shorter DMFS in TNBC treated with chemotherapy (p < 0.01). This study provides evidence of an association between TRIM2 and poor patient outcomes in TNBC, especially those treated with chemotherapy. The molecular mechanisms and functional behaviour of TRIM2 and the functional link with GLS in BC warrant further exploration using in vitro models.

Influence of an Intrinsically Disordered Region on Protein Domains Revealed by NMR-Based Electrostatic Potential Measurements.

Many human proteins possess intrinsically disordered regions containing consecutive aspartate or glutamate residues ("D/E repeats"). Approximately half of them are DNA/RNA-binding proteins. In this study, using nuclear magnetic resonance (NMR) spectroscopy, we investigated the electrostatic properties of D/E repeats and their influence on folded domains within the same protein. Local electrostatic potentials were directly measured for the HMGB1 protein, its isolated D/E repeats, and DNA-binding domains by NMR. The data provide quantitative information about the electrostatic interactions between distinct segments of HMGB1. Due to the interactions between the D/E repeats and the DNA-binding domains, local electrostatic potentials of the DNA-binding domains within the full-length HMGB1 protein were largely negative despite the presence of many positively charged residues. Our NMR data on counterions and electrostatic potentials show that the D/E repeats and DNA have similar electrostatic properties and compete for the DNA-binding domains. The competition promotes dissociation of the protein-DNA complex and influences the molecular behavior of the HMGB1 protein. These effects may be general among the DNA/RNA-binding proteins with D/E repeats.

Molecular Orientation Behavior of Lyotropic Liquid Crystal-Carbon Dot Hybrids in Microfluidic Confinement.

Lyotropic liquid crystals represent an important class of anisotropic colloid systems. Their integration with optically active nanoparticles can provide us with responsive luminescent media that offer new fundamental and applied solutions for biomedicine. This paper analyzes the molecular-level behavior of such composites represented by tetraethylene glycol monododecyl ether and nanoscale carbon dots in microfluidic channels. Microfluidic confinement allows for simultaneously applying multiple factors, such as flow dynamics, wall effects, and temperature, for the precise control of the molecular arrangement in such composites and their resulting optical properties. The microfluidic behavior of composites was characterized by a set of analytical and modeling tools such as polarized and fluorescent microscopy, dynamic light scattering, and fluorescent spectroscopy, as well as image processing in Matlab. The composites were shown to form tunable anisotropic intermolecular structures in microchannels with several levels of molecular ordering. A predominant lamellar structure of the composites was found to undergo additional ordering with respect to the microchannel axis and walls. Such an alignment was controlled by applying shear and temperature factors to the microfluidic environment. The revealed molecular behavior of the composite may contribute to the synthesis of hybrid organized media capable of polarized luminescence for on-chip diagnostics and biomimetics.

Knockdown of SCN5A alters metabolic-associated genes and aggravates hypertrophy in the cardiomyoblast.

SCN5A mutations have been reported to cause various cardiomyopathies in humans. Most of the SCN5A mutations causes loss of function and thereby, alters the overall cellular function. Therefore, to understand the loss of SCN5A function in cardiomyocytes, we have knocked down the SCN5A gene (SCN5A-KD) in H9c2 cells and explored the cell phenotype and molecular behaviors in the presence and absence of isoproterenol (ISO), an adrenergic receptor agonist that induces cardiac hypertrophy. Expression of several genes related to hypertrophy, inflammation, fibrosis, and energy metabolism pathways were evaluated. It was found that the mRNA expression of hypertrophy-related gene, brain (B-type) natriuretic peptide (BNP) was significantly increased in SCN5A-KD cells as compared to 'control' H9c2 cells. There was a further increase in the mRNA expressions of BNP and βMHC in SCN5A-KD cells after ISO treatment compared to their respective controls. Pro-inflammatory cytokine, tumor necrosis factor-alpha expression was significantly increased in 'SCN5A-KD' H9c2 cells. Further, metabolism-related genes like glucose transporter type 4, cluster of differentiation 36, peroxisome proliferator-activated receptor alpha, and peroxisome proliferator-activated receptor-gamma were significantly elevated in the SCN5A-KD cells as compared to the control cells. Upregulation of these metabolic genes is associated with increased ATP production. The study revealed that SCN5A knock-down causes alteration of gene expression related to cardiac hypertrophy, inflammation, and energy metabolism pathways, which may promote cardiac remodelling and cardiomyopathy.

Investigating the Effect of Liver Regeneration on Tumor Growth: Development of a Mouse Model with Orthotopic Implantation of Patient-derived HCC Organoids

Abstract Background Recurrence after hepatocellular carcinoma (HCC) treatment is a significant problem. It affects more than 70% of patients undergoing liver resection. Recurrence can arise from undetected micro metastasis or de novo cancer. Clinical and experimental studies suggest that liver regeneration ensuing surgical resection may activate occult micro-metastasis leading to regeneration induced tumor recurrence. However, in vivo patient-derived organoid (PDO) HCC models that are translatable to patient tumors are sparse. Aims Here, we aim to establish a new in vivo model to understand the impact of liver regeneration on HCC tumor growth. Methods PDOs were generated from HCC tissue obtained from patients undergoing liver resection at the Clarunis University Digestive Health and Care Center and transduced with firefly luciferase. Implantation was performed via laparotomy and orthotopic injection of the organoids in the right superior liver lobe. Tumor growth is monitored by in vivo bioluminescence imaging until the endpoint of the experiment. As a primary endpoint tumor growth two weeks after liver resection was defined. Experimental groups underwent either minor (30%) or major (65%) hepatectomy of tumor-free liver, whereas the control group received a re-laparotomy with subsequent closure of the abdomen. Normal liver and tumor tissue were characterized using immunohistochemistry. Results Two HCC-PDO lines were successfully implanted. Compared to the control, after minor and major liver resection the mean weight increased significantly to 0.82% (p &amp;lt; 0.0001) respectively 0.99% (p &amp;lt; 0.0001). Preliminary data about the tumor volume have yet to be concluded. Histology and immunohistochemistry staining for HCC confirmed the origin of the PDOs from the original patient tumor. Conclusion The establishment of an orthotopic xenograft mouse model for HCC PDO was successful. Through liver resection, a regenerative environment could be achieved, to investigate the molecular behavior of HCC recurrence after surgery. This offers the basis to study potential new targets and mechanisms to improve HCC-treatment.

Molecular evaluation and genetic behavior of white tip nematode resistance against Aphelenchoides besseyi in artificially infected rice plants

Genetic behavior of some morphological, yield and its related traits was studied under nematode infection condition using five rice genotypes which were crossed using complete-diallel analysis to produce 20 rice hybrids. All 25 genotypes were evaluated under both normal and white tip nematode infection conditions. Although, molecular evaluation using simple sequence repeats for characters related to resistance were done. As a result of this study, the parental varieties Giza179, Giza182 and Sakha105 were the best of all parents, since they possessed favorite general combining ability (GCA) effects for many traits. The three crosses Sakha106 × Sakha101, Sakha105 × Sakha101 and Giza182 × Giza179 recorded the desirable values of specific combining ability (SCA) for most of the studied traits. Dominance genetic variance played the most significant role in inheritance of the traits under study. The two crosses Sakha101 × Sakha106 and Sakha105 × Sakha101 were considered the best for yield and its components under affected condition by white tip nematode. RM5526 marker was the best in detecting genetic diversity among the rice accessions for the resistance-associated trait, no. Of Aphelenchoides besseyi (A. besseyi) individuals in 100 grains (NA). While, RM161 marker was the best in detecting genetic diversity among the rice accessions for the resistance-associated trait, loss rate of panicle weight (LRPW). Principal component analysis (PCA) was applied for morpho-physiological characters and molecular data analysis and showed a good separation of the genotypes which was in high agreement with phylogenetic tree clustering and also showed that SSR analysis can be recognized with the help of principal component analysis, which are accountable for the observed genotypic variations presented within each component. Two DNA fragments with molecular size of 165 bp and 146 bp may play an important role in the white tip nematode resistance in rice while they appeared only in the resistant parents and crosses. These bands should be isolated, sequenced and compared with the genes in data base which are responsible for white tip nematode resistance in rice. Both DNA fragments will be of great interest in nematode resistance programs in rice in the future. Finally, we can recommend the farmers to use the two varieties Giza 179 and Giza182 for planting in land affected with white tip nematode. The farmers could also be recommend to use the two hybrids Sakha106 × Sakha105 and Giza179 × Sakha105 when planting in land affected with white tip nematode while they proved to be resistant to white tip nematode by using morphological and molecular analyses. For researchers we can recommend by using the two specific molecular markers, RM5526 and RM161 for fast identification of white tip nematode resistant rice varieties in Egypt.

BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to the low micrometric size range. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in the secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. In more detail, the dimer formation achieved by molecular self-docking showed two distinct poses, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.