A Bioinformatics Method for the Production of Antibody-Drug Conjugates Through Site-Specific Cysteine Conjugation

Antibody-drug conjugates (ADCs) have emerged as a promising class of targeted anticancer therapy, and it is distinguished from traditional chemotherapeutic ap‐ proaches by its potential to kill cancer cells with limited side effects. Site-specific conjugation is one of the current challenges in ADC development because it allows for controlled conjugation and production of homogeneous ADCs. This chapter describes a computational method for the generation of antibody-drug conjugates as PDB files through site-specific cysteine conjugation, given the PDB files of a drug, a linker, and an antibody. The drug and linker are reconfigured using the rotation and translation functions of an affine transformation, which is brought in appropriate positions for the bonds to occur between the three molecules. The hydrogen and disulfide bonds are employed to connect the linker and drug as well as the linker with the antibody, respectively. Examples of conjugates produced with the presented method have been demonstrated.