Molecular Systems Design & Engineering最新文献

{"title":"Dual responsive fluorescence switching of organohydrogel towards base/acid†","authors":"Manish Kumar Dixit, Moupia Mukherjee, Bharat Kumar Sahu, Abul Kalam and Mrigendra Dubey","doi":"10.1039/D4ME00067F","DOIUrl":"https://doi.org/10.1039/D4ME00067F","url":null,"abstract":"<p >Herein, we have synthesized an ESIPT inbuilt novel tripodal gelator <strong>TH-AIL</strong>, which upon dissolution in DMSO followed by the addition of water (1 : 1) leads to the formation of a unique orange fluorescent organohydrogel (0.35% w/v, OHG). The obtained OHG reveals responses towards base NH<small>₃</small> and acid HCl by way of reversible change in fluorescence colour from orange to green along with restorable conversion from gel to sol phase.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1210-1214"},"PeriodicalIF":3.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising vaccine models against astrovirus MLB2 using integrated vaccinomics and immunoinformatics approaches†","authors":"Syed Luqman Ali, Awais Ali, Waseef Ullah, Asifullah Khan, Elham Mohammed Khatrawi, Abdul Malik, Aigul Abduldayeva, Aliya Baiduissenova, Hind Jaber Althagafi and Deema Fallatah","doi":"10.1039/D3ME00192J","DOIUrl":"https://doi.org/10.1039/D3ME00192J","url":null,"abstract":"<p >Astrovirus MLB2 (AstV-MLB2) is an emerging gastrointestinal virus causing meningitis and disseminated infections. Currently, there are no vaccine-based therapies available for AstV-MLB2. This study aims to develop multi-epitope vaccine models using candidate proteins from AstV-MLB2. Highly immunogenic epitopes (IC<small>₅₀</small> &lt; 200 μM) exhibiting conservation, antigenicity, and non-allergenicity were called from these proteins. Additionally, the selection criteria for epitopes were based on their potential to trigger immune cells and stimulate IFN-γ-mediated immune responses. The model vaccine constructs were designed from identified lead epitopes, along with immune-enhancer adjuvants and linker sequences. The proposed vaccine models were assessed for allergenicity, antigenicity, and structural integrity to ensure their safety and effectiveness. The binding potential of the vaccine models to HLA and TLR-4 immune cell receptors was evaluated to identify their capacity to stimulate immune responses. Among several raw constructs, MLB2-V1 and MLB2-V2 were identified as potential vaccine candidates due to their non-allergenic features, enhanced antigenic properties, and structural stability. Both these constructs were extensively evaluated and predicted to effectively bind to and interact with immune cell receptors, potentially triggering cellular and innate immune responses. Additionally, the prioritized constructs were deemed suitable for cloning and expression using recombinant DNA systems. The model vaccine constructs showed promise, warranting further investigation into their immune efficacy against MLB2-mediated infections through experimental assays and clinical trials.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1285-1299"},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Graph-based networks for accurate prediction of ground and excited state molecular properties from minimal features†","authors":"Denish Trivedi, Kalyani Patrikar and Anirban Mondal","doi":"10.1039/D4ME00113C","DOIUrl":"https://doi.org/10.1039/D4ME00113C","url":null,"abstract":"<p >Graph neural networks (GNN) have been demonstrated to correlate molecular structure with properties, enabling rapid evaluation of molecules for a given application. Molecular properties, including ground and excited states, are crucial to analyzing molecular behavior. However, while attention-based mechanisms and pooling methods have been optimized to accurately predict specific properties, no versatile models can predict diverse molecular properties. Here, we present graph neural networks that predict a wide range of properties with high accuracy. Model performance is high regardless of dataset size and origin. Further, we demonstrate an implementation of hierarchical pooling enabling high-accuracy prediction of excited state properties by effectively weighing aspects of features that correlate better with target properties. We show that graph attention networks consistently outperform convolution networks and linear regression, particularly for small dataset sizes. The graph attention model is more accurate than previous message-passing neural networks developed for the prediction of diverse molecular properties. Hence, the model is an efficient tool for screening and designing molecules for applications that require tuning multiple molecular properties.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1275-1284"},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-consistent field theory and coarse-grained molecular dynamics simulations of pentablock copolymer melt phase behavior†","authors":"So Jung Park, Tristan Myers, Vinson Liao and Arthi Jayaraman","doi":"10.1039/D4ME00138A","DOIUrl":"https://doi.org/10.1039/D4ME00138A","url":null,"abstract":"<p >Block copolymer (BCP) self-assembly leads to nanostructured materials with diverse ordered morphologies, some of which are attractive for transport applications. Multiblock AB copolymers are of interest as they offer a larger design parameter space than diblock copolymers allowing researchers to tailor their self-assembly to achieve target morphologies. In this study, we investigate the phase behavior of symmetric A<small>_<em>x</em></small>B<small>_<em>y</em></small>A<small>_<em>z</em></small>B<small>_<em>y</em></small>A<small>_<em>x</em></small> and B<small>_<em>x</em></small>A<small>_<em>y</em></small>B<small>_<em>z</em></small>A<small>_<em>y</em></small>B<small>_<em>x</em></small> pentablock copolymers (pentaBCPs) where A and B monomers have the same statistical segment length. We use a combination of self-consistent field theory (SCFT) calculations and molecular dynamics (MD) simulations to link the polymer design parameters, namely the fraction of middle block volume to the volume of all blocks of same type, <em>τ</em>, overall volume fraction of A block, <em>f</em><small>_A</small>, and segregation strength, <em>χN</em>, to the equilibrium morphologies and the distributions of chain conformations in these morphologies. In the phase diagrams calculated using SCFT, we observe broader double gyroid windows and the existence of lamellar morphologies even at small values <em>f</em><small>_A</small> in contrast to what has been seen for diblock copolymers. We also see a reentrant phase sequence of double gyroid → cylinder → lamellae → cylinder → double gyroid with increasing <em>τ</em> at fixed <em>f</em><small>_A</small>. The chain conformations adopted in these morphologies are sampled in coarse-grained MD simulations and quantified with distributions of the chain end-to-end distance and fractions of chains whose middle (A or B) and end (A or B) blocks remain within domains of same chemistry (A or B). These analyses show that the pentaBCP chains adopt “looping”, “bridging”, and “hybrid” (both looping and bridging) conformations, with a majority of the chains adopting the hybrid conformation. The spatial distributions for each of the blocks in the pentaBCPs show that blocks of the same type in a chain locally segregate within the same domains, with shorter blocks segregating towards the domain boundaries and longer blocks filling the domain interior. This combined SCFT-MD approach enables us to rapidly screen the extensive pentaBCP design space to identify design rules for transport-favorable morphologies as well as verify the chain conformations and spatial arrangements associated with the theory predicted reentrant phase behavior.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1235-1253"},"PeriodicalIF":3.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/me/d4me00138a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular design of protein-based materials – state of the art, opportunities and challenges at the interface between materials engineering and synthetic biology","authors":"Ebony Shire, André A. B. Coimbra, Carlos Barba Ostria, Leonardo Rios-Solis and Diego López Barreiro","doi":"10.1039/D4ME00122B","DOIUrl":"10.1039/D4ME00122B","url":null,"abstract":"<p >Structural proteins like silk, squid ring teeth, elastin, collagen, or resilin, among others, are inspiring the development of new sustainable biopolymeric materials for applications including healthcare, food, soft robotics, or textiles. Furthermore, advances in the fields of soft materials and synthetic biology have a joint great potential to guide the design of novel structural proteins, despite both fields progressing mostly in a separate fashion so far. Using recombinant DNA technologies and microbial fermentations, we can design new structural proteins with monomer-level sequence control and a dispersity of <em>ca.</em> 1.0, based on permutations of tandem repeats derived from natural structural proteins. However, the molecular design of recombinant and repetitive structural proteins is a nontrivial task that is generally approached using low-throughput trial-and-error experimentation. Here, we review recent progress in this area, in terms of structure–function relationships and DNA synthesis technologies. We also discuss experimental and computational advances towards the establishment of rapid prototyping pipelines for this family of biopolymers. Finally, we highlight future challenges to make protein-based materials a commercially viable alternative to current fossil-based polymers.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1187-1209"},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/me/d4me00122b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-site esterification: a tunable, reversible strategy to tailor therapeutic peptides for delivery†","authors":"Mark S. Bannon, Jeffrey F. Ellena, Aditi S. Gourishankar, Spencer R. Marsh, Dilza Trevisan-Silva, Nicholas E. Sherman, L. Jane Jourdan, Robert G. Gourdie and Rachel A. Letteri","doi":"10.1039/D4ME00072B","DOIUrl":"10.1039/D4ME00072B","url":null,"abstract":"<p >Peptides are naturally potent and selective therapeutics with massive potential; however, low cell membrane permeability limits their clinical implementation, particularly for hydrophilic, anionic peptides with intracellular targets. To overcome this limitation, esterification of anionic carboxylic acids on therapeutic peptides can simultaneously increase hydrophobicity and net charge to facilitate cell internalization, whereafter installed esters can be cleaved hydrolytically to restore activity. To date, however, most esterified therapeutics contain either a single esterification site or multiple esters randomly incorporated on multiple sites. This investigation provides molecular engineering insight into how the number and position of esters installed onto the therapeutic peptide α carboxyl terminus 11 (αCT11, RPRPDDLEI) with 4 esterification sites affect hydrophobicity and the hydrolysis process that reverts the peptide to its original form. After installing methyl esters onto αCT11 using Fischer esterification, we isolated 5 distinct products and used 2D nuclear magnetic resonance spectroscopy, reverse-phase high performance liquid chromatography, and mass spectrometry to determine which residues were esterified in each and the resulting increase in hydrophobicity. We found esterifying the C-terminal isoleucine to impart the largest increase in hydrophobicity. Monitoring ester hydrolysis showed the C-terminal isoleucine ester to be the most hydrolytically stable, followed by the glutamic acid, whereas esters on aspartic acids hydrolyze rapidly. LC-MS revealed the formation of transient intramolecular aspartimides prior to hydrolysis to carboxylic acids. <em>In vitro</em> proof-of-concept experiments showed esterifying αCT11 to increase cell migration into a scratch, highlighting the potential of multi-site esterification as a tunable, reversible strategy to enable the delivery of therapeutic peptides.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1215-1227"},"PeriodicalIF":3.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/me/d4me00072b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling the photochromism of zirconium pyromellitic diimide-based metal–organic frameworks through coordinating solvents†","authors":"Youcong Li, Jiahao Dong, Yue Zhao, Lei Gao, Yu-Hao Gu and Shuai Yuan","doi":"10.1039/D4ME00104D","DOIUrl":"10.1039/D4ME00104D","url":null,"abstract":"<p >Metal–organic frameworks (MOFs) are promising platforms for designing photoresponsive materials due to their structural versatility and tunable properties. However, challenges remain in fine-tuning the photoresponsive behavior while maintaining the high stability of MOFs. In this study, we synthesized a MOF containing redox-active pyromellitic diimide (PMDI) groups and unsaturated Zr<small>₆</small> clusters named Zr-PMDI-DMF and fine-tuned its photochromic properties by exchanging the coordination solvent molecules on the Zr sites. Unlike traditional Zr<small>₆</small> clusters with bidentate carboxylate coordination, Zr-PMDI-DMF features monodentate carboxylate coordination with the exposed Zr sites occupied by solvent molecules. We post-synthetically exchanged the coordinated <em>N</em>,<em>N</em>-dimethylformamide (DMF) solvent molecules with 2-(dimethylamino)ethanol (DMAE), <em>N</em>-methyltetrahydropyrrole (NMP), and dimethyl sulfoxide (DMSO) and determined the structures of the coordinated solvent molecules using single-crystal X-ray diffraction. Through photochromic and bleaching cycle experiments, electron paramagnetic resonance spectroscopy, and density functional theory calculations, we found that the coordinated solvents act as electron donors. In contrast, PMDI ligands act as electron acceptors, causing intra-framework electron transfer and photochromism. The rate of the photochromic response correlated with the electron-donating ability of the solvents, following the trend of DMAE &gt; NMP &gt; DMSO &gt; DMF.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1228-1234"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the design of optimal computer experiments to model solvent effects on reaction kinetics†","authors":"Lingfeng Gui, Alan Armstrong, Amparo Galindo, Fareed Bhasha Sayyed, Stanley P. Kolis and Claire S. Adjiman","doi":"10.1039/D4ME00074A","DOIUrl":"10.1039/D4ME00074A","url":null,"abstract":"<p >Developing an accurate predictive model of solvent effects on reaction kinetics is a challenging task, yet it can play an important role in process development. While first-principles or machine learning models are often compute- or data-intensive, simple surrogate models, such as multivariate linear or quadratic regression models, are useful when computational resources and data are scarce. The judicious choice of a small set of training data, <em>i.e.</em>, a set of solvents in which quantum mechanical (QM) calculations of liquid-phase rate constants are to be performed, is critical to obtaining a reliable model. This is, however, made especially challenging by the highly irregular shape of the discrete space of possible experiments (solvent choices). In this work, we demonstrate that when choosing a set of computer experiments to generate training data, the D-optimality criterion value of the chosen set correlates well with the likelihood of achieving good model performance. With the Menshutkin reaction of pyridine and phenacyl bromide as a case study, this finding is further verified <em>via</em> the evaluation of the surrogate models regressed using D-optimal solvent sets generated from four distinct selection spaces. We also find that incorporating quadratic terms in the surrogate model and choosing the D-optimal solvent set from a selection space similar to the test set can significantly improve the accuracy of reaction rate constant predictions while using a small training dataset. Our approach holds promise for the use of statistical optimality criteria for other types of computer experiments, supporting the construction of surrogate models with reduced resource and data requirements.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 12","pages":" 1254-1274"},"PeriodicalIF":3.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/me/d4me00074a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective mineralization at hydrogel interface induced by fusion between peptide hydrogels†","authors":"Yongbaek Kim, Hiroto Isobe, Keishi Nishio and Kazuki Murai","doi":"10.1039/D4ME00112E","DOIUrl":"10.1039/D4ME00112E","url":null,"abstract":"<p >Biomineralization has garnered attention not only for its fundamental role in understanding the mechanisms of biomineral formation but also as a method for fabricating next-generation functional materials. In this study, we investigated the nucleation, crystal growth, and particle growth processes of calcium phosphates (CaPs) formed using selective mineralization at the hydrogel interface induced by the fusion of peptide hydrogels. After 1 day of mineralization, band-like white precipitates were observed at the fusion interface of the hydrogels. Notably, the nucleation and crystal growth of the mineralized CaP exhibited different behaviors owing to the differences in the properties of the reaction interface for mineralization. The selective nucleation and crystal growth of the CaPs at the hydrogel interface were attributed to (1) the local concentration of mineral sources near the peptide network, driven by electrostatic interactions between the polar functional groups and mineral source ions, and (2) selective crystal growth of the CaPs induced by the nanostructure of the surface functional groups.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 11","pages":" 1107-1115"},"PeriodicalIF":3.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of amide-bonded supramolecular multifunctional fillers towards boosted self-healing, thermal conductivity and dielectric properties","authors":"Junlong Yao, Zongqiang Fu, Huan Yang, Lin Gao, Xueliang Jiang, Wei Nie, Zhengguang Sun, Haolan Lu, Meiyun Lin and Jinglou Xu","doi":"10.1039/D4ME00114A","DOIUrl":"10.1039/D4ME00114A","url":null,"abstract":"<p >Multifunctional composites with rapid self-healing performance have been widely applied in various fields. However, different types of fillers result in decreased self-healing efficiency and present agglomeration and poor compatibility especially at high filler contents. Here, based on the different surface modifications of barium titanate (BT) and silicon carbide (SiC) and the amide-bond synergistic effects between these fillers, self-healing supramolecular composites with high filler contents (up to 30%) are reported, and exhibit high strength, dielectric and thermal-conduction properties. Modification significantly improves the dispersion of these fillers, and greatly enhances the coexistence and synergy between these fillers. This three-phase amide-bonded supramolecular composite exhibits a high tensile strength of 3.22 MPa compared to other self-healing materials such as self-healing hydrogels, a high dielectric constant of 23, a high thermal conductivity of 0.36 W m<small>⁻¹</small> K<small>⁻¹</small> and a superior self-healing efficiency of above 94%. These performances are ascribed to the formation of amide bonds between the amino groups in 3-aminopropyltriethoxysilane (KH550)-modified silicon carbide (SiC-NH<small>₂</small>) and the carboxyl groups in tartaric acid (TA)-modified barium titanate (BT-TA), which can provide efficient supramolecular interactions between different fillers, as well as more reversible hydrogen bonding for the matrix. This three-phase amide-bonded supramolecular composite provides an effective strategy to improve the self-healing properties of multifunctional composites, and will bring pioneering functions to electronic packaging materials, dielectric energy storage materials, environmental energy and other fields, which can open up broad application prospects.</p>","PeriodicalId":91,"journal":{"name":"Molecular Systems Design & Engineering","volume":" 11","pages":" 1167-1178"},"PeriodicalIF":3.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142209515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}