Updated publication reference for PubMed record(s): 32348883. The structural analysis of proteins and protein complexes is key for understanding their function and regulation. In order to gain structural information, we examined protein surface labelling using NHS-Acetate and DEPC following an MS-based workflow. Using two model proteins we characterise the obtained mass spectra and explore the applicability of a quantitative approach for determining of solvent accessible amino acid residues on the surface of proteins and protein complexes. The modified peptides were analysed by LC-MS/MS and processed using MaxQuant for identification and intensity determination of labelled and unlabelled peptides.