Characterization of small-molecule-biomacromolecule interactions: From simple to complex

The interactions between small molecules and biomacromolecules constitute one of the most important parts of interconnected biological networks. To understand the recognition mechanisms of these interactions is of vital importance for characterizing the expression and the function of related biomacromolecules and further discovering drug candidates for the pharmaceutical industry and biomarkers for clinical diagnosis. Here, we summarize the general methodology used in these studies, mainly including chromatographic, electromigration and mass spectrometric methods. We present the latest applications of these methods for elucidating simple binding of plasma protein, enzyme, receptor and DNA/RNA with small molecules. We also present recognition studies based on multi-component systems (e.g., phage display, oligonucleotides, chemiproteomics and traditional Chinese medicines), which should be more challenging in both analytical tools and methodology and the function of biological systems.