Maximum occurrence of conformations from average data

Claudio Luchinat

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