Inbiochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or other factors; each possible shape is called a conformation, and a transition between them is called a conformational change. Factors that may induce such changes include temperature, pH, voltage, lightinchromophores, concentrationofions, phosphorylation, or the binding of a ligand. Transitions between these states occur on a variety of length scales (tenths of Å to nm) and time scales (ns to s),
and have been linked to functionally relevant phenomena such as allosteric signaling[1] and enzyme catalysis.[2]
A specific nonlinear optical technique called second-harmonic generation (SHG) has been recently applied to the study of conformational change in proteins.[4] In this method, a second-harmonic-active probe is placed at a site that undergoes motion in the protein by mutagenesis or non-site-specific attachment, and the protein is adsorbed or specifically immobilized to a surface. A change in protein conformation produces a change in the net orientation of the dye relative to the surface plane and therefore the intensity of the second harmonic beam. In a protein sample with a well-defined orientation, the tilt angle of the probe can be quantitatively determined, in real space and real time. Second-harmonic-active unnatural amino acids can also be used as probes.[citation needed]
Another method applies electro-switchable biosurfaces where proteins are placed on top of short DNA molecules which are then dragged through a buffer solution by application of alternating electrical potentials. By measuring their speed which ultimately depends on their hydrodynamic friction, conformational changes can be visualized.[citation needed]
X-ray crystallography can provide information about changes in conformation at the atomic level, but the expense and difficulty of such experiments make computational methods an attractive alternative.[7] Normal mode analysis with elastic network models, such as the Gaussian network model, can be used to probe molecular dynamics trajectories as well as known structures.[8][9] ProDy is a popular tool for such analysis.[10]
^Salafsky JS, Cohen B (November 2008). "A second-harmonic-active unnatural amino acid as a structural probe of biomolecules on surfaces". The Journal of Physical Chemistry B. 112 (47): 15103–7. doi:10.1021/jp803703m. PMID18928314.
