Abstract
Cross-linking mass spectrometry (XL-MS) provides low-resolution structural information to model protein structures. Here, we present a protocol to identify cross-links of purified antibody binding to purified human leukocyte antigen (HLA). We describe steps for using a discovery-based XL-MS approach followed by a targeted XL-MS approach. We then detail procedures for using the identified cross-links with other structural data for molecular docking of the antibody to HLA. This protocol has applications for modeling the interacting structure of purified antibody to antigen. For complete details on the use and execution of this protocol, please refer to Ser et al.1.