This invention features methods, systems, and compositions for detecting interactions between biomolecules. The methods or systems of the present invention may feature comparing the amount of labeling or modification of a molecule in a test sample with the amount of labeling or modification of the molecule in a control sample. For example, the method may comprise subjecting the molecule of interest in the sample to a reaction adapted to modify and/or label one or more areas or residues (e.g., amino acids, nucleotides, etc.) of the molecule of interest. The method may further comprise making visible the detectable labels or modifications on the molecule of interest and evaluating the amount of detectable label or modification present in the sample.