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  1. Article: Harnessing Generative AI to Decode Enzyme Catalysis and Evolution for Enhanced Engineering.

    Xie, Wen Jun / Warshel, Arieh

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Enzymes, as paramount protein catalysts, occupy a central role in fostering remarkable progress across numerous fields. However, the intricacy of sequence-function relationships continues to obscure our grasp of enzyme behaviors and curtails our ... ...

    Abstract Enzymes, as paramount protein catalysts, occupy a central role in fostering remarkable progress across numerous fields. However, the intricacy of sequence-function relationships continues to obscure our grasp of enzyme behaviors and curtails our capabilities in rational enzyme engineering. Generative artificial intelligence (AI), known for its proficiency in handling intricate data distributions, holds the potential to offer novel perspectives in enzyme research. By applying generative models, we could discern elusive patterns within the vast sequence space and uncover new functional enzyme sequences. This review highlights the recent advancements in employing generative AI for enzyme sequence analysis. We delve into the impact of generative AI in predicting mutation effects on enzyme fitness, activity, and stability, rationalizing the laboratory evolution of
    Language English
    Publishing date 2023-10-12
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.10.561808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Harnessing generative AI to decode enzyme catalysis and evolution for enhanced engineering.

    Xie, Wen Jun / Warshel, Arieh

    National science review

    2023  Volume 10, Issue 12, Page(s) nwad331

    Abstract: Enzymes, as paramount protein catalysts, occupy a central role in fostering remarkable progress across numerous fields. However, the intricacy of sequence-function relationships continues to obscure our grasp of enzyme behaviors and curtails our ... ...

    Abstract Enzymes, as paramount protein catalysts, occupy a central role in fostering remarkable progress across numerous fields. However, the intricacy of sequence-function relationships continues to obscure our grasp of enzyme behaviors and curtails our capabilities in rational enzyme engineering. Generative artificial intelligence (AI), known for its proficiency in handling intricate data distributions, holds the potential to offer novel perspectives in enzyme research. Generative models could discern elusive patterns within the vast sequence space and uncover new functional enzyme sequences. This review highlights the recent advancements in employing generative AI for enzyme sequence analysis. We delve into the impact of generative AI in predicting mutation effects on enzyme fitness, catalytic activity and stability, rationalizing the laboratory evolution of
    Language English
    Publishing date 2023-12-28
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2745465-4
    ISSN 2053-714X ; 2053-714X
    ISSN (online) 2053-714X
    ISSN 2053-714X
    DOI 10.1093/nsr/nwad331
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Natural Evolution Provides Strong Hints about Laboratory Evolution of Designer Enzymes.

    Xie, Wen Jun / Warshel, Arieh

    Proceedings of the National Academy of Sciences of the United States of America

    2022  Volume 119, Issue 31, Page(s) e2207904119

    Abstract: Laboratory evolution combined with computational enzyme design provides the opportunity to generate novel biocatalysts. Nevertheless, it has been challenging to understand how laboratory evolution optimizes designer enzymes by introducing seemingly ... ...

    Abstract Laboratory evolution combined with computational enzyme design provides the opportunity to generate novel biocatalysts. Nevertheless, it has been challenging to understand how laboratory evolution optimizes designer enzymes by introducing seemingly random mutations. A typical enzyme optimized with laboratory evolution is the abiological Kemp eliminase, initially designed by grafting active site residues into a natural protein scaffold. Here, we relate the catalytic power of laboratory-evolved Kemp eliminases to the statistical energy ([Formula: see text]) inferred from their natural homologous sequences using the maximum entropy model. The [Formula: see text] of designs generated by directed evolution is correlated with enhanced activity and reduced stability, thus displaying a stability-activity trade-off. In contrast, the [Formula: see text] for mutants in catalytic-active remote regions (in which remote residues are important for catalysis) is strongly anticorrelated with the activity. These findings provide an insight into the role of protein scaffolds in the adaption to new enzymatic functions. It also indicates that the valley in the [Formula: see text] landscape can guide enzyme design for abiological catalysis. Overall, the connection between laboratory and natural evolution contributes to understanding what is optimized in the laboratory and how new enzymatic function emerges in nature, and provides guidance for computational enzyme design.
    MeSH term(s) Catalysis ; Catalytic Domain ; Directed Molecular Evolution ; Entropy ; Enzymes/metabolism ; Mutation ; Protein Engineering
    Chemical Substances Enzymes
    Language English
    Publishing date 2022-07-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2207904119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Electrochemical

    Zhao, Lan / Xie, Wen-Jun / Meng, Zheng-Zheng / Li, Hong-Ru / He, Liang-Nian

    Organic letters

    2024  Volume 26, Issue 15, Page(s) 3241–3246

    Abstract: Herein, we report an electrochemical protocol for the dicarboxylation of aryl alkynes using ... ...

    Abstract Herein, we report an electrochemical protocol for the dicarboxylation of aryl alkynes using CO
    Language English
    Publishing date 2024-04-05
    Publishing country United States
    Document type Journal Article
    ISSN 1523-7052
    ISSN (online) 1523-7052
    DOI 10.1021/acs.orglett.4c00860
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Mononuclear Iron Pyridinethiolate Complex Promoted CO

    Zhang, Yong-Kang / Zhao, Lan / Xie, Wen-Jun / Li, Hong-Ru / He, Liang-Nian

    ChemSusChem

    2024  , Page(s) e202400090

    Abstract: Designing earth-abundant metal complexes as efficient molecular photocatalysts for visible light-driven ... ...

    Abstract Designing earth-abundant metal complexes as efficient molecular photocatalysts for visible light-driven CO
    Language English
    Publishing date 2024-03-01
    Publishing country Germany
    Document type Journal Article
    ISSN 1864-564X
    ISSN (online) 1864-564X
    DOI 10.1002/cssc.202400090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Exploring the Role of Chemical Reactions in the Selectivity of Tyrosine Kinase Inhibitors

    Asadi, Mojgan / Xie, Wen Jun / Warshel, Arieh

    Journal of the American Chemical Society. 2022 Aug. 31, v. 144, no. 36

    2022  

    Abstract: A variety of diseases are associated with tyrosine kinase enzymes that activate many proteins via signal transduction cascades. The similar ATP-binding pockets of these tyrosine kinases make it extremely difficult to design selective covalent inhibitors. ...

    Abstract A variety of diseases are associated with tyrosine kinase enzymes that activate many proteins via signal transduction cascades. The similar ATP-binding pockets of these tyrosine kinases make it extremely difficult to design selective covalent inhibitors. The present study explores the contribution of the chemical reaction steps to the selectivity of the commercialized inhibitor acalabrutinib over the Bruton’s tyrosine kinase (BTK) and the interleukin-2-inducible T-cell kinase (ITK). Ab initio and empirical valence bond (EVB) simulations of the two kinases indicate that the most favorable reaction path involves a water-assisted mechanism of the 2-butynamide reactive group of acalabrutinib. BTK reacts with acalabrutinib with a substantially lower barrier than ITK, according to our calculated free-energy profile and kinetic simulations. Such a difference is due to the microenvironment of the active site, as further supported by a sequence-based analysis of specificity determinants for several commercialized inhibitors. Our study involves a new approach of simulating directly the IC50 and inactivation efficiency kₑff, instead of using the standard formulas. This new strategy is particularly important in studies of covalent inhibitors with a very exothermic bonding step. Overall, our results demonstrate the importance of understanding the chemical reaction steps in designing selective covalent inhibitors for tyrosine kinases.
    Keywords T-lymphocytes ; active sites ; chemical reactions ; commercialization ; heat production ; inhibitory concentration 50 ; phosphotransferases (kinases) ; signal transduction ; tyrosine
    Language English
    Dates of publication 2022-0831
    Size p. 16638-16646.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c07307
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: [The role of mitochondria-associated endoplasmic reticulum membranes in age-related cardiovascular diseases].

    Zhang, Yu / Zhao, Xin-Yi / Xie, Wen-Jun / Zhang, Yi

    Sheng li xue bao : [Acta physiologica Sinica

    2023  Volume 75, Issue 6, Page(s) 799–816

    Abstract: Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the physical connection sites between mitochondria and endoplasmic reticulum (ER). As the compartments controlling substance and information communications between ER and mitochondria, ... ...

    Abstract Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the physical connection sites between mitochondria and endoplasmic reticulum (ER). As the compartments controlling substance and information communications between ER and mitochondria, MAMs were involved in the regulation of various pathophysiological processes, such as calcium homeostasis, mitochondrial morphology and function, lipid metabolism and autophagy. In the past decades, accumulating lines of evidence have revealed the pivotal role of MAMs in diverse cardiovascular diseases (CVD). Aging is one of the major independent risk factors for CVD, which causes progressive degeneration of the cardiovascular system, leading to increased morbidity and mortality of CVD. This review aims to summarize the research progress of MAMs in age-related CVD, and explore new targets for its prevention and treatment.
    MeSH term(s) Humans ; Mitochondrial Membranes ; Cardiovascular Diseases/metabolism ; Calcium Signaling/physiology ; Mitochondria/physiology ; Endoplasmic Reticulum/metabolism
    Language Chinese
    Publishing date 2023-12-27
    Publishing country China
    Document type Review ; English Abstract ; Journal Article
    ZDB-ID 604308-2
    ISSN 0371-0874
    ISSN 0371-0874
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 386: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  8. Article ; Online: Molecular Engineering of Copper Phthalocyanine for CO

    Chen, Jin-Mei / Xie, Wen-Jun / Yang, Zhi-Wen / He, Liang-Nian

    ChemSusChem

    2023  Volume 17, Issue 6, Page(s) e202301634

    Abstract: Efficient electrochemical ... ...

    Abstract Efficient electrochemical CO
    Language English
    Publishing date 2023-11-30
    Publishing country Germany
    Document type Journal Article
    ISSN 1864-564X
    ISSN (online) 1864-564X
    DOI 10.1002/cssc.202301634
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Exploring the Role of Chemical Reactions in the Selectivity of Tyrosine Kinase Inhibitors.

    Asadi, Mojgan / Xie, Wen Jun / Warshel, Arieh

    Journal of the American Chemical Society

    2022  Volume 144, Issue 36, Page(s) 16638–16646

    Abstract: A variety of diseases are associated with tyrosine kinase enzymes that activate many proteins via signal transduction cascades. The similar ATP-binding pockets of these tyrosine kinases make it extremely difficult to design selective covalent inhibitors. ...

    Abstract A variety of diseases are associated with tyrosine kinase enzymes that activate many proteins via signal transduction cascades. The similar ATP-binding pockets of these tyrosine kinases make it extremely difficult to design selective covalent inhibitors. The present study explores the contribution of the chemical reaction steps to the selectivity of the commercialized inhibitor acalabrutinib over the Bruton's tyrosine kinase (BTK) and the interleukin-2-inducible T-cell kinase (ITK). Ab initio and empirical valence bond (EVB) simulations of the two kinases indicate that the most favorable reaction path involves a water-assisted mechanism of the 2-butynamide reactive group of acalabrutinib. BTK reacts with acalabrutinib with a substantially lower barrier than ITK, according to our calculated free-energy profile and kinetic simulations. Such a difference is due to the microenvironment of the active site, as further supported by a sequence-based analysis of specificity determinants for several commercialized inhibitors. Our study involves a new approach of simulating directly the IC50 and inactivation efficiency
    MeSH term(s) Agammaglobulinaemia Tyrosine Kinase ; Benzamides/pharmacology ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology ; Pyrazines ; Tyrosine
    Chemical Substances Benzamides ; Protein Kinase Inhibitors ; Pyrazines ; Tyrosine (42HK56048U) ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2) ; acalabrutinib (I42748ELQW)
    Language English
    Publishing date 2022-08-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/jacs.2c07307
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Bonn / Germany

    Z 4' 55/32: Show issues
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  10. Article: Thyroidectomy using a single-port cervico-mental angle approach.

    Li, Hua-Shui / Lin, Qiang / Xie, Wen-Jun

    Journal of minimal access surgery

    2022  Volume 18, Issue 4, Page(s) 585–590

    Abstract: Background: Over the last two decades, several endoscopic thyroidectomy methods have been developed. However, there are some limitations in these procedures. To date, the optimal surgical approach for thyroid cancer has not yet been developed. This ... ...

    Abstract Background: Over the last two decades, several endoscopic thyroidectomy methods have been developed. However, there are some limitations in these procedures. To date, the optimal surgical approach for thyroid cancer has not yet been developed. This study reported the surgical operation steps, clinical outcomes, and experience of 30 patients who underwent trans-cervico-mental angle single-port endoscopic thyroidectomy (TCMASPET) at our centre.
    Patients and methods: A total of 30 patients were enrolled in the present study. Patients underwent unilateral or bilateral thyroidectomy through a cervico-mental angle incision of 2.48 ± 0.31 cm, after which the lymphoid adipose tissues in the central region were dissected.
    Results: All surgeries were successfully completed. Two patients underwent bilateral thyroid carcinoma resection with bilateral central region lymph node dissection, 23 patients received unilateral thyroid cancer resection with unilateral central region lymph node dissection, four patients underwent unilateral thyroid resection, and one patient received bilateral thyroid resection with unilateral central region lymph node dissection. No permanent post-operative complications were observed.
    Conclusions: TCMASPET was a safe and feasible approach that was relatively easy to perform. This approach may expand the indications for endoscopic thyroidectomy while maintaining excellent cosmetic outcomes.
    Language English
    Publishing date 2022-10-07
    Publishing country India
    Document type Journal Article
    ZDB-ID 2186884-0
    ISSN 1998-3921 ; 0972-9941
    ISSN (online) 1998-3921
    ISSN 0972-9941
    DOI 10.4103/jmas.jmas_276_21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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