Molecular Dynamics Simulations with NAMD and Trajectory Analysis

Molecular simulations offer a window into proteins' movements, which other methods fail to measure. The fractional, slight modifications of structure seen, for example, in molecular breathing, or movements which are so fast as to evade wet lab detection, are made accessible through the use of high-powered computing to drive simulations. While simulations are theoretical, they rely largely on real-world data, utilizing solved crystal, cryo-EM, or SAXS structures as starting points. These can be used either for the simulation directly or for homology modeling to aid in the solving of novel structures and proteins. Simulations are run in parallel with increased power and altered conditions, allowing even unusual or rare event structures to be seen and studied, which may be missed by wet lab techniques. The data generated can then be corroborated in the wet laboratory through biophysical techniques, measuring the larger movements. The ability to discern discrete structures and complex movements becomes most useful for structurally promiscuous, multi-domain proteins. This description suits well the ADAMTS family of proteins, which have been shown to have multiple structures, cryptic epitopes, and high levels of glycosylation. Therefore, we present a method by which one can explore the structures generated by ADAMTS13 using MD.