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Protein Engineering Design & Selection最新文献

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Antibody numbering schemes: advances, comparisons and tools for antibody engineering. 抗体编号方案：抗体工程的进展、比较和工具。
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2025-04-01 DOI: 10.1093/protein/gzaf005
Zirui Zhu, Hossein Ashrafian, Navid Mohammadian Tabrizi, Emily Matas, Louisa Girard, Haowei Ma, Edouard C Nice
{"title":"Antibody numbering schemes: advances, comparisons and tools for antibody engineering.","authors":"Zirui Zhu, Hossein Ashrafian, Navid Mohammadian Tabrizi, Emily Matas, Louisa Girard, Haowei Ma, Edouard C Nice","doi":"10.1093/protein/gzaf005","DOIUrl":"https://doi.org/10.1093/protein/gzaf005","url":null,"abstract":"<p><p>The evolution of antibody engineering has significantly enhanced the development of antibody-based therapeutics, enabling the creation of novel antibody formats tailored for specific applications. Since the introduction of the Kabat numbering scheme in 1977, various schemes have been developed and modified, forming the foundation for multiple antibody engineering projects. The tools associated with these schemes further facilitate the engineering process. However, discrepancies among current numbering schemes can lead to confusion. This study examines various numbering schemes and related tools, providing new insights into antibody variable domains. Improved understanding of antibody numbering and related tools holds significant potential for more precise and efficient antibody design, thereby advancing antibody-based therapeutics and diagnostics.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Engineering of a lysosomal-targeted GAA enzyme.
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2025-01-10 DOI: 10.1093/protein/gzaf001
Nicholas Marze, Ilya Tikh, Susan Benard, Yuxing Cheng, Vincent Yu, Waijiao Cai, Edward Lavallie, Erin Lopez, Jing Wang, Tatyana Zamkovaya, Suryanarayan Somanathan
{"title":"Engineering of a lysosomal-targeted GAA enzyme.","authors":"Nicholas Marze, Ilya Tikh, Susan Benard, Yuxing Cheng, Vincent Yu, Waijiao Cai, Edward Lavallie, Erin Lopez, Jing Wang, Tatyana Zamkovaya, Suryanarayan Somanathan","doi":"10.1093/protein/gzaf001","DOIUrl":"10.1093/protein/gzaf001","url":null,"abstract":"<p><p>Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme. We also demonstrate the ablation of binding between our modified IGF-II tag and two off-target receptors: IGF-I receptor and insulin receptor, as well as preserved enzymatic activity of the chimeric GAA molecule.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CDRxAbs: antibody small-molecule conjugates with computationally designed target-binding synergy.
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2025-01-10 DOI: 10.1093/protein/gzaf004
Jingzhou Wang, Aiden J Aceves, Nicholas J Friesenhahn, Stephen L Mayo
{"title":"CDRxAbs: antibody small-molecule conjugates with computationally designed target-binding synergy.","authors":"Jingzhou Wang, Aiden J Aceves, Nicholas J Friesenhahn, Stephen L Mayo","doi":"10.1093/protein/gzaf004","DOIUrl":"10.1093/protein/gzaf004","url":null,"abstract":"<p><p>Bioconjugates as therapeutic modalities combine the advantages and offset the disadvantages of their constituent parts to achieve a refined spectrum of action. We combine the concept of bioconjugation with the full atomic simulation capability of computational protein design to define a new class of molecular recognition agents: CDR-extended antibodies, abbreviated as CDRxAbs. A CDRxAb incorporates a covalently attached small molecule into an antibody/target binding interface using computational protein design to create an antibody small-molecule conjugate that binds tighter to the target of the small molecule than the small molecule would alone. CDRxAbs are also expected to increase the target binding specificity of their associated small molecules. In a proof-of-concept study using monomeric streptavidin/biotin pairs at either a nanomolar or micromolar-level initial affinity, we designed nanobody-biotin conjugates that exhibited >20-fold affinity improvement against their protein targets with step-wise optimization of binding kinetics and overall protein stability. The workflow explored through this process promises a novel approach to optimize small-molecule based therapeutics and to explore new chemical and target space for molecular-recognition agents in general.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tuning ProteinMPNN to reduce protein visibility via MHC Class I through direct preference optimization.
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2025-01-10 DOI: 10.1093/protein/gzaf003
Hans-Christof Gasser, Diego A Oyarzún, Javier Antonio Alfaro, Ajitha Rajan
{"title":"Tuning ProteinMPNN to reduce protein visibility via MHC Class I through direct preference optimization.","authors":"Hans-Christof Gasser, Diego A Oyarzún, Javier Antonio Alfaro, Ajitha Rajan","doi":"10.1093/protein/gzaf003","DOIUrl":"10.1093/protein/gzaf003","url":null,"abstract":"<p><p>ProteinMPNN is widely used in protein design workflows due to its ability to identify amino acid sequences that fold into specific 3D protein structures. In our work, we adjust ProteinMPNN to design proteins for a given 3D protein structure with reduced immune-visibility to cytotoxic T lymphocytes that recognize proteins via the MHC-I pathway. To achieve this, we developed a novel framework that integrates direct preference optimization (DPO)-a tuning method originally designed for large language models-with MHC-I peptide presentation predictions. This approach fosters the generation of designs with fewer MHC-I epitopes while preserving the protein's original structure. Our results demonstrate that DPO effectively reduces MHC-I visibility without compromising the structural integrity of the proteins.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimized single-cell gates for yeast display screening. 优化单细胞门酵母显示筛选。
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2025-01-10 DOI: 10.1093/protein/gzae018
Xiaoli Pan, Matheus O de Souza, Francisco M Figueiras, Aric Huang, Bailey B Banach, Jacy R Wolfe, Azady Pirhanov, Bharat Madan, Brandon J DeKosky
{"title":"Optimized single-cell gates for yeast display screening.","authors":"Xiaoli Pan, Matheus O de Souza, Francisco M Figueiras, Aric Huang, Bailey B Banach, Jacy R Wolfe, Azady Pirhanov, Bharat Madan, Brandon J DeKosky","doi":"10.1093/protein/gzae018","DOIUrl":"10.1093/protein/gzae018","url":null,"abstract":"<p><p>Yeast display is a widely used technology in antibody discovery and protein engineering. The cell size of yeast enables fluorescence-activated cell sorting (FACS) to precisely screen gene libraries, including for multi-parameter selection of protein phenotypes. However, yeast cells show a broader size distribution than mammalian cells that complicates single-cell gate determination for FACS. In this report, we analyze several yeast display gating options in detail and present an optimized strategy to select single yeast cells via flow cytometry. These data reveal optimized single-cell gating strategies to support robust and high-efficiency yeast display studies.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enhancing the Thermostability and solubility of a single-domain catalytic antibody.
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2025-01-10 DOI: 10.1093/protein/gzaf002
Yunhang Cui, Xuchen Zhou, Sainan Li, Jingfei Chen, Mingming Qin, Liaoyuan An, Yefei Wang, Lishan Yao
{"title":"Enhancing the Thermostability and solubility of a single-domain catalytic antibody.","authors":"Yunhang Cui, Xuchen Zhou, Sainan Li, Jingfei Chen, Mingming Qin, Liaoyuan An, Yefei Wang, Lishan Yao","doi":"10.1093/protein/gzaf002","DOIUrl":"10.1093/protein/gzaf002","url":null,"abstract":"<p><p>Catalytic antibodies have the ability to bind to and degrade antigens, offering a significant potential for therapeutic use. The light chain of an antibody, UA15-L, can cleave the peptide bond of Helicobacter pylori urease, thus inhibiting the spread of the bacteria. However, the variable domain of UA15-L has a poor thermostability and solubility. In this study, we employed a combined computational and experimental approach to enhance the protein's stability and solubility properties. The protein unfolding hotspots were initially identified using molecular dynamics simulations. Following this, a disulfide bond was designed in an unfolding hotspot to stabilize the protein. Subsequently, protein solubility was enhanced with the assistance of computational methods by introducing polar or charged residues on the protein surface. The combination of multiple mutations resulted in UA15-L variable domain variants with improved thermostability, solubility, expression, and enhanced activity at elevated temperatures. These variants represent promising candidates for further engineering of catalytic activity and specificity.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Growing ecosystem of deep learning methods for modeling protein-protein interactions. 更正：用于蛋白质-蛋白质相互作用建模的深度学习方法生态系统日益壮大。
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2024-01-29 DOI: 10.1093/protein/gzae016
{"title":"Correction to: Growing ecosystem of deep learning methods for modeling protein-protein interactions.","authors":"","doi":"10.1093/protein/gzae016","DOIUrl":"https://doi.org/10.1093/protein/gzae016","url":null,"abstract":"","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":"37 ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Variable heavy-variable light domain and Fab-arm CrossMabs with charged residue exchanges to enforce correct light chain assembly. 更正为可变重型-可变轻型结构域和带电荷残基交换的 Fab 臂 CrossMabs，以执行正确的轻链组装。
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2024-01-29 DOI: 10.1093/protein/gzae017
{"title":"Correction to: Variable heavy-variable light domain and Fab-arm CrossMabs with charged residue exchanges to enforce correct light chain assembly.","authors":"","doi":"10.1093/protein/gzae017","DOIUrl":"https://doi.org/10.1093/protein/gzae017","url":null,"abstract":"","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":"37 ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computational methods for protein design. 蛋白质设计计算方法
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2024-01-29 DOI: 10.1093/protein/gzae011
Noelia Ferruz, Amelie Stein
{"title":"Computational methods for protein design.","authors":"Noelia Ferruz, Amelie Stein","doi":"10.1093/protein/gzae011","DOIUrl":"10.1093/protein/gzae011","url":null,"abstract":"","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An engineered NKp46 antibody for construction of multi-specific NK cell engagers. 用于构建多特异性 NK 细胞吞噬体的工程化 NKp46 抗体。
IF 2.6 4区 生物学
Protein Engineering Design & Selection Pub Date : 2024-01-29 DOI: 10.1093/protein/gzae013
Robert B Lee, Sainiteesh Maddineni, Madeleine Landry, Celeste Diaz, Aanya Tashfeen, Sean A Yamada-Hunter, Crystal L Mackall, Corinne Beinat, John B Sunwoo, Jennifer R Cochran
{"title":"An engineered NKp46 antibody for construction of multi-specific NK cell engagers.","authors":"Robert B Lee, Sainiteesh Maddineni, Madeleine Landry, Celeste Diaz, Aanya Tashfeen, Sean A Yamada-Hunter, Crystal L Mackall, Corinne Beinat, John B Sunwoo, Jennifer R Cochran","doi":"10.1093/protein/gzae013","DOIUrl":"10.1093/protein/gzae013","url":null,"abstract":"<p><p>Recent developments in cancer immunotherapy have highlighted the potential of harnessing natural killer (NK) cells in the treatment of neoplastic malignancies. Of these, bispecific antibodies, and NK cell engager (NKCE) protein therapeutics in particular, have been of interest. Here, we used phage display and yeast surface display to engineer RLN131, a unique cross-reactive antibody that binds to human, mouse, and cynomolgus NKp46, an activating receptor found on NK cells. RLN131 induced proliferation and activation of primary NK cells, and was used to create bispecific NKCE constructs of varying configurations and valency. All NKCEs were able to promote greater NK cell cytotoxicity against tumor cells than an unmodified anti-CD20 monoclonal antibody, and activity was observed irrespective of whether the constructs contained a functional Fc domain. Competition binding and fine epitope mapping studies were used to demonstrate that RLN131 binds to a conserved epitope on NKp46, underlying its species cross-reactivity.</p>","PeriodicalId":54543,"journal":{"name":"Protein Engineering Design & Selection","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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