Structure: Large-scale Studies of Macromolecular Motions

We were amongst the first groups to study macromolecular motions statistically, on a large-scale. In particular, we have set up a publicly accessible Database of Macromolecular Motions and coupled it with simulation tools to interpolate between structural conformations; the database also has associated tools to predict likely motions based on simple models, such as normal modes and localized hinges connecting rigid domains. These allowed us to classify motions based on the interdigitating packing at internal interfaces: motions are identified as shear or hinge, based on whether or not a well-packed interface is maintained between the dynamic elements throughout the motion. This classification scheme is motivated by the fact that protein interiors are packed exceedingly tightly and that tight packing greatly constrains a protein's mobility. We have developed tools for measuring and comparing the packing efficiency at different interfaces and locations throughout macromolecules (e.g. inter-domain, protein surface, helix-helix, protein vs. RNA) using specialized geometric constructions. For this we have generated new protein packing parameters, including self-consistent radii and standard volumes for each atom type.