In Silico Engineering Towards Enhancement of Bap-VHH Monoclonal Antibody Binding Affinity

摘要

Antibodies play major role in immunotherapy, basic researches, and industrial processes. Interactions between antibody-antigen complexes are important to know how they function that help improve their properties in designing new antibodies through rational engineering for therapeutic or biotechnological applications, including the production of biosensors. Nowadays, antibody engineering is widely used in many fields such as medicine, criminal sciences, military, defense industries, etc. Designing antibodies with desired properties is a challenging task. Computational docking is the method of predicting the conformation of a complex structure such as antibody-antigen from its separated elements. The validation of designed antibodies is carried out by docking tools. In the previous study we produced VHH against Bap antigen in Acinetobacter baumannii using phage display technique. In this study, the VHH selected using phage display technique was modeled and docked with its antigen. We made an attempt to find the important amino acids of this antibody, then replaced these amino acids with others to improve their binding affinity of antibody variants to antigens. In this regard, the VHH was mutated. Docking structural prediction of Bap-VHH complex was used for designing and validation of VHHs with higher affinity for binding to Bap receptor. By analysis of the model, several mutants of VHH were designed, and their properties improved in a predictable manner especially for their binding ability to Bap. In conclusion, the designed nanobodies, considering their binding site on Bap, were found to be potential candidates for the treatment of Acinetobacter baumannii infections.