Chemical cross-linking is an attractive technique for the study of the structure of protein complexes due to its low sample consumption and short analysis time. Furthermore, distance constraints obtained from the identification of cross-linked peptides by mass spectrometry can be used to construct and validate protein models. If a sufficient number of distance constraints are obtained, then determining the secondary structure of a protein can allow inference of the protein’s fold. In this work, we show how the distance constraints obtained from cross-linking experiments can identify secondary structures within the protein sequence. Molecular modeling of alpha helices and beta sheets indicate cross-linking patterns based on the topological distances between reactive residues. DSS[1] cross-linking experiments with model alpha helix containing proteins corroborated the molecular modeling predictions. The patterns established here can be extended to other cross-linkers with known spacing lengths.