Integration of FIRST, FRODA and NMM in a coarse grained method to study Protein Disulphide Isomerase conformational change

Our simulations of protein motion are based on a rigidity-based coarse graining criteria which is able to identify flexible and constraint regions and on Normal Modes of Motion (NMM) which map out the directions of motion for a given network. The NMM and rigidity constraints are integrated together by the FRODA module to identify large scale conformational changes at low computational cost. In this context we identify the limits for conformational change of a large multi domain protein -Protein Disulphide Isomerase, by re-assessing the principal NMM at intermediate points along a trajectory as the protein moves over the trajectory defined by the initial principal NMM.