Learning allosteric interactions in Gα proteins from molecular dynamics simulations DOI Open Access

Yi‐Ping Yu,

Maohua Yang, Wenning Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Abstract Gα is a key subunit of heterotrimeric guanine-nucleotide-binding regulatory proteins, yet its conformational dynamics are not fully understood. In this study, we developed Transformer-based graph neural network framework, Dynamic-Mixed Transformer (DMFormer), to investigate Gαo. DMFormer achieved an AUC 0.75 on the training set, demonstrating robustness in distinguishing active and inactive states. The interpretability model was enhanced using integrated gradients, identifying Switch II as critical motif stabilizing state revealing distinct movement patterns between GTPase α-Helix domains. Our findings suggest that rigidity Q205L mutant segment leads persistent activation. Overall, our study showcases effective tool for analyzing protein dynamics, offering valuable insights into activation mechanisms protein.

Язык: Английский

Application of Transformers in Cheminformatics DOI Creative Commons
Kha-Dinh Luong, Ambuj K. Singh

Journal of Chemical Information and Modeling, Год журнала: 2024, Номер 64(11), С. 4392 - 4409

Опубликована: Май 30, 2024

By accelerating time-consuming processes with high efficiency, computing has become an essential part of many modern chemical pipelines. Machine learning is a class methods that can discover patterns within data and utilize this knowledge for wide variety downstream tasks, such as property prediction or substance generation. The complex diverse space requires machine architectures great power. Recently, models based on transformer have revolutionized multiple domains learning, including natural language processing computer vision. Naturally, there been ongoing endeavors in adopting these techniques to the domain, resulting surge publications short period. diversity structures, use cases, necessitate comprehensive summarization existing works. In paper, we review recent innovations adapting transformers solve problems chemistry. Because complex, structure our discussion representations. Specifically, highlight strengths weaknesses each representation, current progress architectures, future directions.

Язык: Английский

Процитировано

10

Research on Bitter Peptides in the Field of Bioinformatics: A Comprehensive Review DOI Open Access

Shanghua Liu,

Tianyu Shi,

Junwen Yu

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9844 - 9844

Опубликована: Сен. 12, 2024

Bitter peptides are small molecular produced by the hydrolysis of proteins under acidic, alkaline, or enzymatic conditions. These can enhance food flavor and offer various health benefits, with attributes such as antihypertensive, antidiabetic, antioxidant, antibacterial, immune-regulating properties. They show significant potential in development functional foods prevention treatment diseases. This review introduces diverse sources bitter discusses mechanisms bitterness generation their physiological functions taste system. Additionally, it emphasizes application bioinformatics peptide research, including establishment improvement databases, use quantitative structure–activity relationship (QSAR) models to predict thresholds, latest advancements classification prediction built using machine learning deep algorithms for identification. Future research directions include enhancing diversifying models, applying generative advance towards deepening discovering more practical applications.

Язык: Английский

Процитировано

3

Computational methods for modeling protein–protein interactions in the AI era: Current status and future directions DOI
Hao Li, Chandran Nithin, Sebastian Kmiecik

и другие.

Drug Discovery Today, Год журнала: 2025, Номер unknown, С. 104382 - 104382

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0

Predicting mutation-disease associations through protein interactions via deep learning DOI Creative Commons
X. Li, Ben Cao,

Jianmin Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 8, 2024

ABSTRACT Disease is one of the primary factors affecting life activities, with complex etiologies often influenced by gene expression and mutation. Currently, wet-lab experiments have analyzed mechanisms mutations, but these are usually limited costs wet constraints in sample types scales. Therefore, this paper constructs a real-world mutation-induced disease dataset proposes Capsule networks Graph topology multi-head attention (CGM) to predict mutation-disease associations. CGM can accurately protein associations, order further elucidate pathogenicity we also verified that mutations lead structural alterations Swiss-model, which suggests conformational changes may be an important pathogenic factor. Limited size mutated dataset, performed on benchmark imbalanced datasets, where mined 22 unknown interaction pairs from better illustrating potential predicting In summary, curates real mutations-disease providing novel tool for understanding biomolecular pathways mechanisms.

Язык: Английский

Процитировано

1

BioStructNet: Structure-Based Network with Transfer Learning for Predicting Biocatalyst Functions DOI Creative Commons
Xiangwen Wang, Jiahui Zhou,

Jessica Mueller

и другие.

Journal of Chemical Theory and Computation, Год журнала: 2024, Номер unknown

Опубликована: Дек. 20, 2024

Enzyme–substrate interactions are essential to both biological processes and industrial applications. Advanced machine learning techniques have significantly accelerated biocatalysis research, revolutionizing the prediction of biocatalytic activities facilitating discovery novel biocatalysts. However, limited availability data for specific enzyme functions, such as conversion efficiency stereoselectivity, presents challenges accuracy. In this study, we developed BioStructNet, a structure-based deep network that integrates protein ligand structural capture complexity enzyme–substrate interactions. Benchmarking studies with different algorithms showed enhanced predictive accuracy BioStructNet. To further optimize small set, implemented transfer in framework, training source model on large set fine-tuning it small, function-specific using CalB case study. The performance was validated by comparing attention heat maps generated BioStructNet interaction module revealed from molecular dynamics simulations complexes. would accelerate functional enzymes use, particularly cases where sets small.

Язык: Английский

Процитировано

1

BioStructNet: Structure-Based Network with Transfer Learning for Predicting Biocatalyst Functions DOI Open Access
Xiangwen Wang, Jiahui Zhou,

Jessica Mueller

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 18, 2024

Abstract Enzyme-substrate interactions are essential to both biological processes and industrial applications. Advanced machine learning techniques have significantly accelerated biocatalysis research, revolutionizing the prediction of biocatalytic activities facilitating discovery novel biocatalysts. However, limited availability data for specific enzyme functions, such as conversion efficiency stereoselectivity, presents challenges accuracy. In this study, we developed BioStructNet, a structure-based deep network that integrates protein ligand structural capture complexity enzyme-substrate interactions. Benchmarking studies with different algorithms showed enhanced predictive accuracy BioStructNet. To further optimize small dataset, implemented transfer in framework, training source model on large dataset fine-tuning it small, function-specific using CalB case study. The performance was validated by comparing attention heat maps generated BioStructNet interaction module, substrate revealed complexes from molecular simulations. would accelerate functional enzymes use, particularly cases where datasets small.

Язык: Английский

Процитировано

0

Learning allosteric interactions in Gα proteins from molecular dynamics simulations DOI Open Access

Yi‐Ping Yu,

Maohua Yang, Wenning Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Abstract Gα is a key subunit of heterotrimeric guanine-nucleotide-binding regulatory proteins, yet its conformational dynamics are not fully understood. In this study, we developed Transformer-based graph neural network framework, Dynamic-Mixed Transformer (DMFormer), to investigate Gαo. DMFormer achieved an AUC 0.75 on the training set, demonstrating robustness in distinguishing active and inactive states. The interpretability model was enhanced using integrated gradients, identifying Switch II as critical motif stabilizing state revealing distinct movement patterns between GTPase α-Helix domains. Our findings suggest that rigidity Q205L mutant segment leads persistent activation. Overall, our study showcases effective tool for analyzing protein dynamics, offering valuable insights into activation mechanisms protein.

Язык: Английский

Процитировано

0