Abstract
AbstractEffective responses against different immune challenges require secretion of antibodies with various isotypes performing specific effector functions. Structural information on these isotypes is essential to engineer antibodies with desired physico-chemical features of their antigen-binding properties, and optimal stability and developability as potential therapeutic antibodies.In silicomutational scanning profiles on antibody structures would further pinpoint candidate mutations for enhancing antibody stability and function. Although a number of antibody structure databases exist, a public data resource which provides clear, consistent annotation of isotypes, species coverage of 3D antibody structures and their deep mutation profiles is currently lacking. TheVandCregion bearingantibody (VCAb) web tool is established with the purpose to clarify these annotations and provide an accessible and easily consultable resource to facilitate antibody engineering. VCAb currently provides data on 6,948 experimentally determined antibody structures including both V and C regions from different species. Additionally, VCAb provides annotations of species and isotypes with both V and C region numbering schemes applied, which can be interactively queried or downloaded in batch. Multiplein silicomutational scanning methods are applied on VCAb structures to provide an easily accessible interface for querying the impact of mutations on antibody stability. These features are implemented in a R shiny application to enable interactive data interrogation. VCAb is freely accessible athttps://fraternalilab.cs.ucl.ac.uk/VCAb/. The source code to generate the VCAb database and the online R shiny application is available athttps://github.com/Fraternalilab/VCAb, enabling users to set up local VCAb instances.
Publisher
Cold Spring Harbor Laboratory