Aggrescan4D : A comprehensive tool for pH-dependent analysis and engineering of protein aggregation propensity
Zalewski, Mateusz (University of Warsaw)
Iglesias, Valentin (Universitat Autònoma de Barcelona)
Bárcenas, Oriol (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Ventura, Salvador (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Kmiecik, Sebastian (University of Warsaw)
Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular

Date:	2024
Abstract:	Aggrescan4D (A4D) is an advanced computational tool designed for predicting protein aggregation, leveraging structural information and the influence of pH. Building upon its predecessor, Aggrescan3D (A3D), A4D has undergone numerous enhancements aimed at assisting the improvement of protein solubility. This manuscript reviews A4D's updated functionalities and explains the fundamental principles behind its pH-dependent calculations. Additionally, it presents an antibody case study to evaluate its performance in comparison with other structure-based predictors. Notably, A4D integrates advanced protein engineering protocols with pH-dependent calculations, enhancing its utility in advising solubility-enhancing mutations. A4D considers the impact of structural flexibility on aggregation propensities, and includes a large set of precalculated predictions. These capabilities should help to open new avenues for both understanding and managing protein aggregation. A4D is accessible through a dedicated web server at https://biocomp. chem. uw. edu. pl/a4d/.
Grants:	Agencia Estatal de Investigación PID2022-137963OB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-00635
Note:	Altres ajuts: acords transformatius de la UAB; Polish National Agency for Academic Exchange under the ULAM NAWA Programme (BPN/ULM/2023/1/00189/U/00001); National Science Center (Sheng2021/40/Q/NZ2/00078)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Computational biology ; Monoclonal antibodies ; Ph-dependent aggregation ; Protein aggregation ; Protein engineering ; Protein solubility ; Protein stability ; Structural bioinformatics
Published in:	Protein science, Vol. 33, Num. 10 (september 2024) , ISSN 1469-896X

DOI: 10.1002/pro.5180
PMID: 39324697

17 p, 19.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles