A protocol for information-driven antibody-antigen modelling with the HADDOCK2.4 webserver

TL;DR

This paper presents a computational protocol using the HADDOCK 2.4 webserver for predicting antibody-antigen complex structures, aiding therapeutic antibody design by leveraging structural modeling and docking strategies.

Contribution

It introduces a detailed, step-by-step protocol for antibody-antigen docking with HADDOCK 2.4, incorporating hypervariable loop identification and epitope information.

Findings

Protocol enables accurate antibody-antigen complex modeling

Guidelines adapt to available epitope data

Facilitates therapeutic antibody development

Abstract

In the recent years, therapeutic use of antibodies has seen a huge growth, due to their inherent proprieties and technological advances in the methods used to study and characterize them. Effective design and engineering of antibodies for therapeutic purposes are heavily dependent on knowledge of the structural principles that regulate antibody-antigen interactions. Several experimental techniques such as X-ray crystallography, cryo-electron microscopy, NMR or mutagenesis analysis can be applied, but these are usually expensive and time consuming. Therefore computational approaches like molecular docking may offer a valuable alternative for the characterisation of antibody-antigen complexes. Here we describe a protocol for the prediction of the 3D structure of antibody-antigen complexes using the integrative modelling platform HADDOCK. The protocol consists of: 1) The identification of the antibody residues belonging to the hyper variable loops which are known to be crucial for the binding and can be used to guide the docking; 2) The detailed steps to perform docking with the HADDOCK 2.4 webserver following different strategies depending on the availability of information about epitope residues.