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AB-Panda: An AI-Generated Antibody Structure-Based Tool for Developability Prediction
Wu Zou1, Jianjun Deng2, Yun Shen2
1School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan Province, China.
The developability of antibodies is a critical concern in antibody discovery, encompassing issues such as self-interaction, aggregation, and thermal stability. The use of computational and structure-based tools has greatly improved the evaluation and prioritization of initial antibody sequences. With the increasing demand for subcutaneous administration of small-volume, high-concentration antibody formulations, there is a need for more accurate prediction tools based on protein structures. Our study introduces AB-Panda, a tool based on AlphaFold2-predicted antibody structures and three innovative structure-related metrics. AB-Panda utilizes unit-area hydrophobic value (UHV), unit-area positive charge (UPC), and unit-area negative charge (UNC) to automatically identify hydrophobic and charged patches within the complementarity determining regions (CDRs) of antibodies. Through the analysis of the 919 clinical stage therapeutic (CST) antibodies, we have established recommended ranges of UHV, UPC, and UNC as reference standards for antibody developability. AB-Panda offers clear visualizations of surface hydrophobic and charge distribution, facilitating the identification of problematic amino acids and providing suggestions for further sequence engineering. Additionally, AB-Panda has been integrated into a web application, available at https://www.antibodydev.com, by combining UHV, UPC, UNC, and other established computational metrics for the early screening and optimization of antibody sequences.
The developability of antibodies is a critical concern in antibody discovery, encompassing issues such as self-interaction, aggregation, and thermal stability. The use of computational and structure-based tools has greatly improved the evaluation and prioritization of initial antibody sequences. With the increasing demand for subcutaneous administration of small-volume, high-concentration antibody formulations, there is a need for more accurate prediction tools based on protein structures. Our study introduces AB-Panda, a tool based on AlphaFold2-predicted antibody structures and three innovative structure-related metrics. AB-Panda utilizes unit-area hydrophobic value (UHV), unit-area positive charge (UPC), and unit-area negative charge (UNC) to automatically identify hydrophobic and charged patches within the complementarity determining regions (CDRs) of antibodies. Through the analysis of the 919 clinical stage therapeutic (CST) antibodies, we have established recommended ranges of UHV, UPC, and UNC as reference standards for antibody developability. AB-Panda offers clear visualizations of surface hydrophobic and charge distribution, facilitating the identification of problematic amino acids and providing suggestions for further sequence engineering. Additionally, AB-Panda has been integrated into a web application, available at https://www.antibodydev.com, by combining UHV, UPC, UNC, and other established computational metrics for the early screening and optimization of antibody sequences.
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Antibody Structure
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibody Structure and Classes
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.

