8cc42982c826e53a28b9052aad92bf99 NucAciRes_a2024v52pW170.pdf 8d061ffdff6958e15bea9e75c2d8db11aa3fff6c NucAciRes_a2024v52pW170.pdf 667f2377f6414c51b7ffd73b4ae32a9a6b4c37fd95141a6fb1422e4e022fc8b0 NucAciRes_a2024v52pW170.pdf Title: Aggrescan4D: structure-informed analysis of pH-dependent protein aggregation Subject: DOI: 10.1093/nar/gkae382 , 52, Web Server issue, 13-5-2024. Abstract: Protein aggregation is behind the genesis of incurable diseases and imposes constraints on drug discovery and the industrial production and formulation of proteins. Over the years, we have been advancing the Aggresscan3D (A3D) method, aiming to deepen our comprehension of protein aggregation and assist the engineering of protein solubility. Since its inception, A3D has become one of the most popular structure-based aggregation predictors because of its performance, modular functionalities, RESTful service for extensive screenings, and intuitive user interface. Building on this foundation, we introduce Aggrescan4D (A4D), significantly extending A3D’s functionality. A4D is aimed at predicting the pH-dependent aggregation of protein structures, and features an evolutionary-informed automatic mutation protocol to engineer protein solubility without compromising structure and stability. It also integrates precalculated results for the nearly 500,000 jobs in the A3D Model Organisms Database and structure retrieval from the AlphaFold database. Globally, A4D constitutes a comprehensive tool for understanding, predicting, and designing solutions for specific protein aggregation challenges. The A4D web server and extensive documentation are available at https://biocomp.chem.uw.edu.pl/a4d/. This website is free and open to all users without a login requirement. Keywords: Author: Brcenas Oriol, Kuriata Aleksander, Zalewski Mateusz, Iglesias Valentn, Pintado-Grima Carlos, Firlik Grzegorz, Burdukiewicz Micha, Kmiecik Sebastian, Ventura Salvador Creator: OUP Producer: Acrobat Distiller 24.0 (Windows); modified using iTextSharp 5.5.10 ©2000-2016 iText Group NV (AGPL-version) CreationDate: Fri Jun 28 07:29:49 2024 CEST ModDate: Thu Jun 5 17:26:19 2025 CEST Custom Metadata: yes Metadata Stream: yes Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 6 Encrypted: no Page size: 612 x 792 pts (letter) Page rot: 0 File size: 898852 bytes Optimized: no PDF version: 1.4 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FHAJNP+RMTMI Type 1C Custom yes yes yes 47 0 FHAJNO+SabonLTStd-Bold Type 1C Custom yes yes yes 169 0 FHAJAC+UniversLTStd-Light Type 1C Custom yes yes yes 115 0 FHAHKK+UniversLTStd-BoldCn Type 1C Custom yes yes yes 723 0 FHAHKJ+UniversLTStd-Bold Type 1C Custom yes yes yes 45 0 FHAHKI+UniversLTStd-Cn Type 1C Custom yes yes yes 724 0 FHAHKH+UniversLTStd-CnObl Type 1C Custom yes yes yes 725 0 FHAHKG+dummy-space Type 1C WinAnsi yes yes no 48 0 FHAHKF+SabonLTStd-Roman Type 1C Custom yes yes yes 49 0 GPKQIG+ArialMT TrueType WinAnsi yes yes no 1 0 FHAJPB+UniversLTStd Type 1C Custom yes yes yes 44 0 FHAJPA+UniversLTStd-Obl Type 1C Custom yes yes yes 46 0 FHAKIO+MTSY Type 1C Custom yes yes yes 103 0 FHALNH+Helvetica-Bold Type 1C WinAnsi yes yes no 116 0 FHAMHE+SabonLTStd-Italic Type 1C Custom yes yes yes 168 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-06-06 02:55:53 CEST RepresentationInformation: NucAciRes_a2024v52pW170.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-06-05 17:28:30 CEST Size: 898852 Format: PDF Version: 1.4 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Tagged PDF PDFMetadata: Objects: 1000 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: true NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: OneColumn PageMode: UseThumbs Language: English Outlines: Item: Title: Graphical abstract Destination: section.2.2.0 Item: Title: Introduction Destination: section.3.3.0 Item: Title: New features and updates Destination: section.4.4.0 Item: Title: Limitations Destination: section.5.8.0 Item: Title: Discussion and conclusions Destination: section.6.9.0 Item: Title: Data availability Destination: section.7.10.0 Item: Title: Supplementary data Destination: section.8.11.0 Item: Title: Funding Destination: section.9.12.0 Item: Title: Conflict of interest statement Destination: section.10.13.0 Item: Title: References Destination: section.11.13.0 Info: Title: Aggrescan4D: structure-informed analysis of pH-dependent protein aggregation Author: Brcenas Oriol, Kuriata Aleksander, Zalewski Mateusz, Iglesias Valentn, Pintado-Grima Carlos, Firlik Grzegorz, Burdukiewicz Micha, Kmiecik Sebastian, Ventura Salvador Subject: DOI: 10.1093/nar/gkae382 , 52, Web Server issue, 13-5-2024. Abstract: Protein aggregation is behind the genesis of incurable diseases and imposes constraints on drug discovery and the industrial production and formulation of proteins. Over the years, we have been advancing the Aggresscan3D (A3D) method, aiming to deepen our comprehension of protein aggregation and assist the engineering of protein solubility. Since its inception, A3D has become one of the most popular structure-based aggregation predictors because of its performance, modular functionalities, RESTful service for extensive screenings, and intuitive user interface. Building on this foundation, we introduce Aggrescan4D (A4D), significantly extending A3D’s functionality. A4D is aimed at predicting the pH-dependent aggregation of protein structures, and features an evolutionary-informed automatic mutation protocol to engineer protein solubility without compromising structure and stability. It also integrates precalculated results for the nearly 500,000 jobs in the A3D Model Organisms Database and structure retrieval from the AlphaFold database. Globally, A4D constitutes a comprehensive tool for understanding, predicting, and designing solutions for specific protein aggregation challenges. The A4D web server and extensive documentation are available at https://biocomp.chem.uw.edu.pl/a4d/. This website is free and open to all users without a login requirement. 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