Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 21, 2024
Language: Английский
ACS Central Science, Journal Year: 2024, Volume and Issue: 10(8), P. 1442 - 1459
Published: July 22, 2024
Limited understanding of human proteoforms with complex posttranslational modifications and the underlying mechanisms poses a major obstacle to research on health disease. This Outlook discusses opportunities challenges
Language: Английский
Citations
13
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: March 17, 2024
Protein language models trained on evolutionary data have emerged as powerful tools for predictive problems involving protein sequence, structure, and function. However, these overlook decades of research into biophysical factors governing We propose Mutational Effect Transfer Learning (METL), a model framework that unites advanced machine learning modeling. Using the METL framework, we pretrain transformer-based neural networks simulation to capture fundamental relationships between energetics. finetune experimental sequence-function harness signals apply them when predicting properties like thermostability, catalytic activity, fluorescence. excels in challenging engineering tasks generalizing from small training sets position extrapolation, although existing methods train remain many types assays. demonstrate METL's ability design functional green fluorescent variants only 64 examples, showcasing potential biophysics-based engineering.
Language: Английский
Citations
11
Cell Systems, Journal Year: 2025, Volume and Issue: 16(3), P. 101236 - 101236
Published: March 1, 2025
Highlights•TeleProt is a method for combining evolutionary and assay data to design novel proteins•TeleProt achieved an improved hit rate diversity compared with directed evolution•TeleProt discovered nuclease enzyme 11-fold-improved specific activity•Zero-shot showed higher relative error-prone PCRSummaryOptimizing enzymes function in chemical environments central goal of synthetic biology, but optimization often hindered by rugged fitness landscape costly experiments. In this work, we present TeleProt, machine learning (ML) framework that blends experimental diverse protein libraries, employ it improve the catalytic activity degrades biofilms accumulate on chronic wounds. After multiple rounds high-throughput experiments, TeleProt found significantly better top-performing than evolution (DE), had at finding diverse, high-activity variants, was even able high-performance initial library using no prior data. We have released dataset 55,000 one most extensive genotype-phenotype landscapes date, drive further progress ML-guided design. A record paper's transparent peer review process included supplemental information.Graphical abstract
Language: Английский
Citations
1
The Science of The Total Environment, Journal Year: 2025, Volume and Issue: 974, P. 179206 - 179206
Published: March 29, 2025
Language: Английский
Citations
1
Nature Reviews Bioengineering, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 17, 2024
Language: Английский
Citations
8
Chemical Communications, Journal Year: 2024, Volume and Issue: 60(76), P. 10451 - 10463
Published: Jan. 1, 2024
Biocatalysts that are eco-friendly, sustainable, and highly specific have great potential for applications in the production of fine chemicals, food, detergents, biofuels, pharmaceuticals, more.
Language: Английский
Citations
7
Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(18), P. 10577 - 10617
Published: Aug. 29, 2024
Over the past two decades, genetic code expansion (GCE)-enabled methods for incorporating noncanonical amino acids (ncAAs) into proteins have significantly advanced field of synthetic biology while also reaping substantial benefits from it. On one hand, they provide biologists with a powerful toolkit to enhance and diversify biological designs beyond natural constraints. Conversely, has not only propelled development ncAA incorporation through sophisticated tools innovative strategies but broadened its potential applications across various fields. This Review delves methodological advancements primary site-specific cellular ncAAs in biology. The topics encompass expanding codon addition, creating semiautonomous autonomous organisms, designing regulatory elements, manipulating extending peptide product biosynthetic pathways. concludes by examining ongoing challenges future prospects GCE-enabled highlighting opportunities further this rapidly evolving field.
Language: Английский
Citations
7
ChemBioChem, Journal Year: 2024, Volume and Issue: 25(13)
Published: May 7, 2024
Recent advances in bioeconomy allow a holistic view of existing and new process chains enable novel production routines continuously advanced by academia industry. All this progress benefits from growing number prediction tools that have found their way into the field. For example, automated genome annotations, for building model structures proteins, structural protein methods such as AlphaFold2
Language: Английский
Citations
6
JACS Au, Journal Year: 2024, Volume and Issue: 4(8), P. 3170 - 3182
Published: Aug. 12, 2024
In this study, we present the first example of using a machine learning (ML)-assisted design strategy to optimize synthesis formulation enzyme/ZIFs (zeolitic imidazolate framework) for enhanced performance. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were chosen as model enzymes, while Zn(eIM)2 (eIM = 2-ethylimidazolate) was selected ZIF test our ML-assisted workflow paradigm. Through an iterative ML-driven training-design-synthesis-measurement workflow, efficiently discovered GOx/ZIF (G151) HRP/ZIF (H150) with their overall performance index (OPI) values (OPI represents product encapsulation efficiency (E in %), retained enzymatic activity (A thermal stability (T %)) at least 1.3 times higher than those systematic seed data studies. Furthermore, advanced statistical methods derived from trained random forest qualitatively quantitatively reveal relationship among synthesis, structure, enzyme/ZIF system, offering valuable guidance future studies on enzyme/ZIFs. Overall, proposed holds promise accelerating development other enzyme immobilization systems biocatalysis applications beyond, including drug delivery sensing, others.
Language: Английский
Citations
6
Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)
Published: Dec. 5, 2024
Abstract Bioactive peptides and proteins (BAPPs) are promising therapeutic agents for tissue repair with considerable advantages, including multifunctionality, specificity, biocompatibility, biodegradability. However, the high complexity of microenvironments their inherent deficiencies such as short half-live susceptibility to enzymatic degradation, adversely affect efficacy clinical applications. Investigating fundamental mechanisms by which BAPPs modulate microenvironment developing rational delivery strategies essential optimizing administration in distinct repairs facilitating translation. This review initially focuses on through influence via reactive oxygen species, blood lymphatic vessels, immune cells, cells. Then, a variety platforms, scaffolds hydrogels, electrospun fibers, surface coatings, assisted particles, nanotubes, two-dimensional nanomaterials, nanoparticles engineered summarized incorporate effective repair, modification aimed at enhancing loading efficiencies release kinetics also reviewed. Additionally, can be precisely regulated endogenous stimuli (glucose, enzymes, pH) or exogenous (ultrasound, heat, light, magnetic field, electric field) achieve on-demand tailored specific needs. Furthermore, this potential across various types, bone, cartilage, intervertebral discs, muscle, tendons, periodontal tissues, skin, myocardium, nervous system (encompassing brain, spinal cord, peripheral nerve), endometrium, well ear ocular tissue. Finally, current challenges prospects discussed.
Language: Английский
Citations
6