Maximum occurrence of conformations from average data
CERM/CIRMMP, University of Florence, Italy
In many biologically relevant cases, protein-ligand or protein-protein
recognition occurs thanks to the availability of multiple conformational
states of at least one of the partners. In this talk I will demonstrate that
Paramagnetic NMR is a powerful tool to address the conformational freedom of
proteins. We have developed a rigorous theoretical interpretation of the
average data that permits the characterization of biologically relevant
protein-protein interactions in solution. Besides Paramagnetic NMR data,
other average data such as SAXS can be used, separately or together, in the
analysis, further increasing the power of the method. By our method one can
calculate what we call "Maximum Occurrence", or MO, of any conformation in
an ensemble. It can be empirically shown that the MO of a conformation
correlates with the weight that this conformation has in the ensemble.
Two-domain metalloproteins such as calmodulin or two-domain metalloenzymes
such as matrix metalloproteinases (MMP) are paradigmatic examples. In the
case of MMPs, conformational freedom has been demonstrated recently.
Interdomain flexibility of MMPs can solve the paradox of the ability of MMPs
to "devour" prays such as collagen that are much bigger than MMPs
themselves. The program "MaxOcc" has been developed under the WeNMR grid
infrastructure to allow researchers from outside NMR or SAXS laboratories to
extract this type of information from their own average data.
Date/time: Monday, 22 October 2012, 10:00