The three-dimensional structure of the Fc, needed for assessing the basis for the absence of effector function, was compared with that of IgG2 revealing a number of conformational differences near the hinge region of the CH2 domain that result from the amino acid substitutions.
Application of the limited proteolysis conformational assay to the same protein in purified form and in biological context allowed comparison of conformational differences in vivo and in vitro.
Any disturbances in a protein architecture leads to many kind of abnormalities and intra- or extracellular accumulation of misfolded proteins which are the basis of conformational diseases.
Computational tools to analyze and identify conformational sub-states in the multi-level hierarchy that will enable to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function are still limited.
Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function.
We also provide our views on the predictability of 'open to close' (open→close) transitions of biomolecules on the basis of conformational selection theory.
An alternative method of probing conformational differences involves denaturation of PrPSc in increasing concentrations of guanidine hydrochloride (GdnHCl) [ 9].
It has been demonstrated that DNA cross-links of platinum complexes with enantiomeric amine ligands not only can exhibit different conformational features but also can be processed differently by the cellular machinery as a consequence of these conformational differences.
The lower, light-blue partof each molecule is oriented in the same way in all structures forbetter visualisation of the conformational differences between thecalculated isomers.
The significance of these conformational differences will be discussed below.
