ABSTRACT
The relation between structure and dynamics of biomolecules is important for their functions. Intra-domain dynamics occurring at pico- to milli-second timescales have been shown to correlate with activity. However, the correlation of allosteric communications between domains with biomolecular function is poorly understood. Here we show that inter-domain dynamics of matrix metalloprotease-1 (MMP1) on collagen fibrils are correlated with activity. Using single-molecule FRET, we identified the functionally relevant conformations where the two MMP1 domains are far apart, which were significantly absent for inactive MMP1 and could be modulated by inhibitor and enhancer of activity. All-atom and coarse-grained simulations reproduced the experimental features and revealed that dynamics are similar at pico- and milli-second timescales and substrate-dependent. Functional conformations are accompanied by larger catalytic pocket openings, which are increased by the communications mediated by collagen even if the domain linker is absent. Inter-domain communications are likely important for multidomain proteins in general.