Task 3 - Normal Mode Analysis

Several experimental techniques, such as X-ray crystallography, NMR and spectroscopy, can provide information on the structure and dynamics of biological macromolecules, in our case proteins. However, experimental methods are often time-consuming and do not provide a complete picture of the dynamic properties of proteins. Structural bioinformatics can complement experimental methods.

Molecular dynamics (MD) simulations provide invaluable insight into protein dynamics considering the full range of harmonic and anharmonic motions at the atomic level. However, as you have found out by now, MD simulations are computational expensive. Typical simulations sample conformational motions on the nanosecond timescale.

Normal mode analysis (NMA), on the other hand, has been used successfully to determine and investigate large global motions of proteins. In NMA, the protein is modeled as a harmonic system oscillating around a stable equilibrium. The low-frequency modes correspond to collective motions of the complete protein.

The first NMA of a protein used an all-atom representation of bovine pancreatic trypsin inhibitor (BPTI). You can have a look at the papers here: Brooks & Karplus(1983) Go, Noguti & Nishikawa (1983)

Elastic network models (among them Gaussian and anisotropic network models) greatly reduce the memory requirements for NMA. In 1996, Monique Tirion introduced this simplified model that was further developed by several others during the next years. You can find a short overview here:
http://mmb.pcb.ub.es/FlexServ/help/NMA.php Two original papers can be viewed here: Media:Tirion1996_PRL.pdf Media:Hinsen1998_Proteins.pdf