Aggrescan4D: A Comprehensive Tool for PH-dependent Analysis and Engineering of Protein Aggregation Propensity

Overview

Journal Protein Sci

Specialty Biochemistry

Date 2024 Sep 26

PMID 39324697

Authors

Mateusz Zalewski

Valentin Iglesias

Oriol Barcenas

Salvador Ventura

Sebastian Kmiecik

Affiliations

Soon will be listed here.

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/.

Citing Articles

Aggregating amyloid resources: A comprehensive review of databases on amyloid-like aggregation.

Iglesias V, Chilimoniuk J, Pintado-Grima C, Barcenas O, Ventura S, Burdukiewicz M Comput Struct Biotechnol J. 2024; 23:4011-4018.

PMID: 39582896 PMC: 11585477. DOI: 10.1016/j.csbj.2024.10.047.

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