Bioinformatics Bioinformatics Analysis

Normal Mode Analysis (NMA)

Pinterest LinkedIn Tumblr

Molecular dynamics (MD) and normal mode analysis (NMA) are very useful methods for characterizing many dynamic aspects of biological macromolecules. In comparison to MD, NMA is computationally less expensive which helps in the quick and systematic investigation of protein flexibility and dynamics even for large proteins and protein complexes, whose structure was obtained experimentally or in silico. In particular, NMA can be used to describe the flexible states adopted by a protein around an equilibrium position. These states have been repeatedly shown to have biological relevance and functional significance. 

Normal mode analysis is a technique, based on the physics of small oscillations that can be used to describe the flexible states accessible to a protein around an equilibrium position. The idea is that when an oscillating system at equilibrium, for example a protein in an energy minimum conformation, is slightly perturbed, a restoring force acts to bring the perturbed system back to its equilibrium conformation. A system is defined to be in equilibrium or at the bottom of a potential minimum when the generalized forces acting on it are equal to zero. Despite this, it is still uncommon for NMA to be used as a component of the analysis of a structural study. 

A normal mode shows a resonant motion where all the components of a system are moving with the same frequency and in phase. Normal mode analysis is also known as harmonic analysis and it is based on the assumption that the normal modes with the lowest frequencies are the functionally most relevant modes and they describe the large-scale, overall motion of the protein. 


  • NMA is used to find out the native fluctuations of proteins 
  • NMA particularly highlights the solid state nature of proteins
  • Used for the characterization of the energy landscape related with mechanical unfolding processes
  • NMA can also be used to study the transition paths between two conformations of a protein or to improve protein-ligand docking calculations
  • NMA to address the evolutionary directions of structural changes among homologous proteins of a given superfamily

These uses help in discovering new pathways towards continuum mechanical representations of complex bio-macromolecules.

Single-molecule force spectroscopy by using atomic force microscopy opened up new pathways to get insights into the mechanical unfolding of membrane proteins. Such experiments typically exhibit a characteristic saw-like pattern of the force distance (FD) curves. Since each pattern depends on the protein species, it serves as the unique fingerprint of each molecule. 

Write A Comment