Protein-protein interactions: a supra-structural phenomenon demanding trans-disciplinary biophysical approaches

The study of macromolecular interplays demand biophysical methods interplay. Macromolecular function is mediated via a multitude of energetically defined interactions. Interactions are relevant to study on different time-scales and length-scales, and at different levels of complexity. Hybrid methods, that is, global simultaneous analysis of data from orthogonal methods increase the means to approach the intricate networks of the complex adaptive PPIs at an adequate level. In this imaginative schematic of the diverse aspects of PPIs that can be investigated with hybrid biophysical methodology the colour code is as follows: red: measurable parameters; orange: ab initio SANS/SAXS model; yellow: surface topology elucidated by AFM or cryo-EM; yellow-green/blue sphere pair: FRET labels; green: CCS elucidated by IMS; aqua blue: water!; violet: peptide backbone displaying loop flexibility; pink: surface backbone hydrogens exchanged by deuteriums. This diagram, the lists of parameters and methods are not intended to be exhaustive, rather simply illustrative.