A graph representation of molecular ensembles for polymer property prediction

Chemical Science, Journal Year: 2022, Volume and Issue: 13(35), P. 10486 - 10498

Published: Jan. 1, 2022

Synthetic polymers are versatile and widely used materials. Similar to small organic molecules, a large chemical space of such materials is hypothetically accessible. Computational property prediction virtual screening can accelerate polymer design by prioritizing candidates expected have favorable properties. However, in contrast often not well-defined single structures but an ensemble similar which poses unique challenges traditional representations machine learning approaches. Here, we introduce graph representation molecular ensembles associated neural network architecture that tailored prediction. We demonstrate this approach captures critical features polymeric materials, like chain architecture, monomer stoichiometry, degree polymerization, achieves superior accuracy off-the-shelf cheminformatics methodologies. While doing so, built dataset simulated electron affinity ionization potential values for >40k with varying composition, may be the development other The models presented work pave path toward new classes algorithms informatics and, more broadly, framework modeling ensembles.

Language: Английский

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Applied machine learning as a driver for polymeric biomaterials design

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 10, 2023

Abstract Polymers are ubiquitous to almost every aspect of modern society and their use in medical products is similarly pervasive. Despite this, the diversity commercial polymers used medicine stunningly low. Considerable time resources have been extended over years towards development new polymeric biomaterials which address unmet needs left by current generation medical-grade polymers. Machine learning (ML) presents an unprecedented opportunity this field bypass need for trial-and-error synthesis, thus reducing invested into discoveries critical advancing treatments. Current efforts pioneering applied ML polymer design employed combinatorial high throughput experimental data availability concerns. However, lack available standardized characterization parameters relevant medicine, including degradation biocompatibility, represents a nearly insurmountable obstacle ML-aided biomaterials. Herein, we identify gap at intersection biomedical design, highlight works junction more broadly provide outlook on challenges future directions.

Language: Английский

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Data-Driven Design of Polymer-Based Biomaterials: High-throughput Simulation, Experimentation, and Machine Learning

ACS Applied Bio Materials, Journal Year: 2023, Volume and Issue: 7(2), P. 510 - 527

Published: Jan. 26, 2023

Polymers, with the capacity to tunably alter properties and response based on manipulation of their chemical characteristics, are attractive components in biomaterials. Nevertheless, potential as functional materials is also inhibited by complexity, which complicates rational or brute-force design realization. In recent years, machine learning has emerged a useful tool for facilitating via efficient modeling structure–property relationships domain interest. this Spotlight, we discuss emergence data-driven polymers that can be deployed biomaterials particular emphasis complex copolymer systems. We outline developments, well our own contributions takeaways, related high-throughput data generation polymer systems, methods surrogate learning, paradigms property optimization design. Throughout discussion, highlight key aspects successful strategies other considerations will relevant future polymer-based target properties.

Language: Английский

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Recent Progress in the Endosomal Escape Mechanism and Chemical Structures of Polycations for Nucleic Acid Delivery

Macromolecular Bioscience, Journal Year: 2024, Volume and Issue: 24(4)

Published: Jan. 16, 2024

Abstract Nucleic acid‐based therapies are seeing a spiralling surge. Stimuli‐responsive polymers, especially pH‐responsive ones, gaining widespread attention because of their ability to efficiently deliver nucleic acids. These polymers can be synthesized and modified according target requirements, such as delivery sites the nature In this regard, endosomal escape mechanism polymer–nucleic acid complexes (polyplexes) remains topic considerable interest owing various plausible mechanisms. This review describes current progress in polyplexes state‐of‐the‐art chemical designs for polymers. The importance is also discussed dissociation constant (i.e., p K ) designing new generation along with assays monitor quantify behavior. Further, use machine learning addressed prediction polymer design find novel structures pH responsiveness. will facilitate advanced efficient delivery.

Language: Английский

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Dynamic carriers for therapeutic RNA delivery

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 4, 2024

Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic during to the target tissue across cellular membrane barriers then releasing cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied lipoplexes lipid nanoparticles, over medium-sized sequence-defined xenopeptides, macromolecular polycations polyplexes polymer micelles. This perspective highlights discovery distinct virus-inspired dynamic processes that capitalize on mutual nanoparticle–host interactions achieve potent delivery. From host side, subtle alterations pH, ion concentration, redox potential, presence specific proteins, receptors, or enzymes are cues, which recognized by nanocarrier via designs including cleavable bonds, alterable physicochemical properties, supramolecular assembly–disassembly respond changing biological microenvironment

Language: Английский

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Engineering poly- and micelleplexes for nucleic acid delivery – A reflection on their endosomal escape

Journal of Controlled Release, Journal Year: 2022, Volume and Issue: 353, P. 518 - 534

Published: Dec. 9, 2022

For the longest time, field of nucleic acid delivery has remained skeptical whether or not polycationic drug carrier systems would ever make it into clinical practice. Yet, with disclosure patents on polyethyleneimine-based RNA carriers through leading companies in therapeutics such as BioNTech SE and progress studies beyond phase I trials, this aloofness seems to regress. As one most striking characteristics polymer-based vectors, extraordinary tunability can be both a blessing curse. knowing about adjustment screws how they impact performance provides formulation scientist committed its development head start. Here, we equip reader toolbox - that should advise support developer conceptualize cutting-edge poly- micelleplex system for therapeutic acids; specific, engineer vector towards maximum endosomal escape at minimum toxicity. Therefore, after briefly sketching boundary conditions polymeric design, will dive topic trafficking. We only discuss recent knowledge endo-lysosomal compartment but further depict different hypotheses mechanisms facilitate polyplex systems. Finally, combine facets introduced previous chapters fundamental building blocks polymer design evaluate advantages drawbacks. Throughout article, particular focus placed cellular peculiarities, an additional barrier, also give inspiration cell-specific traits might capitalized on.

Language: Английский

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A User’s Guide to Machine Learning for Polymeric Biomaterials

ACS Polymers Au, Journal Year: 2022, Volume and Issue: 3(2), P. 141 - 157

Published: Nov. 17, 2022

The development of novel biomaterials is a challenging process, complicated by design space with high dimensionality. Requirements for performance in the complex biological environment lead to difficult

Language: Английский

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A high-throughput platform for efficient exploration of functional polypeptide chemical space

Nature Synthesis, Journal Year: 2023, Volume and Issue: 2(6), P. 515 - 526

Published: May 1, 2023

Language: Английский

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Beyond Lipids: Exploring Advances in Polymeric Gene Delivery in the Lipid Nanoparticles Era

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(31)

Published: June 6, 2024

Abstract The recent success of gene therapy during the COVID‐19 pandemic has underscored importance effective and safe delivery systems. Complementing lipid‐based systems, polymers present a promising alternative for delivery. Significant advances have been made in past, with multiple clinical trials progressing beyond phase I several companies actively working on polymeric systems which provides assurance that carriers can soon achieve translation. massive advantage structural tunability vast chemical space is being leveraged to mitigate shortcomings traditional polycationic improve translatability Tailored approaches diverse nucleic acids specific subcellular targets are now designed therapeutic efficacy. This review describes polymer design improved by polyplexes covalent polymer‐nucleic acid conjugates. also offers brief note novel computational techniques design. concludes an overview current state therapies clinic as well future directions their translation clinic.

Language: Английский

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Could artificial intelligence revolutionize the development of nanovectors for gene therapy and mRNA vaccines?

Nano Today, Journal Year: 2022, Volume and Issue: 47, P. 101665 - 101665

Published: Nov. 7, 2022

Language: Английский

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