Probing protein assemblies at the molecular level to understand force-induced conformational changes and interaction dynamics

Proteins interact through complex and dynamic associations, forming assemblies and networks essential for cellular structure, function, and regulation. These dynamic macromolecular complexes rely on structural adaptability and precise interaction networks to maintain functionality under diverse biological conditions. The dynamic interplay of proteins within assemblies and complexes underpins many essential cellular processes, coordinated through multiprotein interactions rather than isolated action of individual proteins. This study investigates the molecular mechanisms underlying protein–protein interactions through computational methods such as force-induced conformational dynamics. The investigation focuses on biologically relevant systems, such as α- and β-tubulin dimerisation, emphasising the effects of small-molecule inhibitors on microtubule assembly, stability, and structural dynamics. In parallel, PROTAC-induced ternary complexes are examined to elucidate cooperative binding effects and the structural and energetic factors that contribute to complex stability. Additionally, the CD47-SIRPα interaction is analysed to relate allelic variation with force-responsive behaviour, enabling extrapolation of variant-specific differences in sustaining cell-surface engagement relevant to immune regulation. The ADP- and DNA-bound forms of SPRTN were comparatively analysed to delineate their roles in structural stabilisation versus catalytic activation. This work demonstrates force-resolved simulation of biomolecular complexes in capturing ligand-dependent conformational changes, variant-specific interaction behaviour, and the structural dynamics underlying biological function and therapeutic relevance.