High-throughput Antibody Screening and Design

With the ability to bind a large variety of molecular targets with high affinity and specificity, antibodies have been used as a key tool to promote the development of isolating, producing, and optimizing these molecules for specific targets of interest. To date, numerous well-established approaches for the discovery of novel antibodies have been developed. As a leading company in the field of antibody discovery, Creative Biolabs is capable of offering high-quality screening and designing service to facilitate the progress of experimental work.

Methods for Antibody Design

Antibody design aims to engineer a new antibody structure that can bind a target of interest, or modify an antibody for enhanced function, such as affinity or thermostability. During the past, several methods such as phage display and immunizing “humanized” mice have been applied for experimental antibody design. However, these techniques require extensive laboratory screenings or advanced analysis to isolate those antibodies actually binding to the intended target. To facilitate the progress of antibody design, new computational methods based on high-throughput screening techniques have been applied to help improve an antibody’s affinity, increase its safety and stability, target new antigens or explore new binding modes. Relying on several tools, including sequence annotation and analysis, structural modeling, function prediction, and mutation, these computational design methods could generate an antibody structure with desired properties, e.g., an antibody with sub-nanomolar binding affinity.

Fig 1. Process of high-throughput based antibody design. (Leem, 2019)

High-throughput Based Antibody Screening and Design

Computational approaches allow a highly controlled parallel screening of multiple biophysical properties in antibody discovery. During computational antibody design, antibody structural modeling is essential because the sequence and structure of the cognate antibody are unknown. Generally, antibody structure prediction is undertaken with a template-based manner as the frameworks of antibody structures are highly conserved. And most methods follow a similar pipeline procedure. Firstly, one or more template structure(s) derived from the Protein Data Bank (PDB) or a curated database to model the framework region are selected and used as a scaffold for subsequent steps. Next, the orientation between the V_H and V_L domains is predicted. Thirdly, the CDR loops are modeled and subsequently, the torsion angles of the side chains are predicted using only the backbone information alone.

Currently, numerous methods have been developed for high-throughput based antibody design. Among these methods, ABodyBuilder and PEARS are widely applied for antibody structural modeling and single amino acid mutation. Particularly, ABodyBuilder could annotate the expected model accuracy. Creative Biolabs is devoted to promoting the development of high-throughput antibody screening and design. With advanced technology platforms, we are able to quickly perform complex calculations and model antibodies for multiple applications, which including but not limited to research, diagnosis, and therapy.

For more detailed information, please feel free to contact us or directly send us a quote.

Reference

1. Leem, J. and Deane, C.M. (2019). “High-Throughput Antibody Structure Modeling and Design Using ABodyBuilder.” Methods Mol Biol, 1851:367-380.

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