Symmetry considerations elucidate the roles of global shape and local interactions in the equilibrium fluctuations and cooperativity of protein assemblies.

Shape had been intuitively recognized to play a dominant role in determining the global motion patterns of bio-molecular assemblies. However, it is not clear exactly how shape determines the motion patterns. What about the local interactions that hold a structure together to a certain shape? The contributions of global shape and local interactions usually mix together and are difficult to tease part. In this work, we use symmetry to elucidate the distinct roles of global shape and local interactions in protein dynamics. Symmetric complexes provide an ideal platform for this task since in them the effects of local interactions and global shape are separable, allowing their distinct roles to be identified. Our key findings based on symmetric assemblies are: (i) the motion patterns of each subunit are determined primarily by intra-subunit interactions (IRSi), and secondarily by inter-subunit interactions (IESi); (ii) the motion patterns of the whole assembly are fully dictated by the global symmetry/shape and have nothing to do with local iESi or IRSi. This is followed by a discussion on how the findings may be generalized to complexes in any shape, with or without symmetry.