crosslinkingeither

Crosslinkingeither is a term used in crosslinking mass spectrometry and structural proteomics to denote a situation in which a single observed crosslink signal is compatible with more than one linkage configuration. It can refer to either different residue pairs linked by a bifunctional crosslinker, or to different reaction pathways or chemistries that could produce matching mass signatures. This ambiguity is most common when using long, symmetric, or multi-kinetic crosslinkers, or when peptide length and sequence context do not constrain the linked sites to a single pair.

In practice, crosslinkingeither is addressed in both experimental design and data analysis. Experimental approaches may employ complementary crosslinkers, protease strategies, or orthogonal measurements to reduce ambiguity. Computationally, the concept is handled by representing the data with multiple possible link configurations and reporting ambiguous crosslinks, often with confidence scores for each alternative. Some workflows aim to resolve either states by integrating additional evidence such as structural constraints, ion mobility, MS3 spectra, or crosslinker cleavage information.

Applications of crosslinkingeither include mapping protein-protein interactions, validating structural models, and generating distance restraints in integrative modelling. The term emphasizes the provisional nature of certain observations and the need for supporting data to distinguish among competing linkage hypotheses. Limitations include increased combinatorial search space, potential false positives if ambiguity is not properly controlled, and dependence on the quality of MS data. Related concepts include crosslinking mass spectrometry, residue-pair identification, and distance-constraint modelling.