Section: Overall Objectives

Highlights of the Year

Our key achievements in 2011 have been twofold.

First, following our work on Voronoi interface models [10] , [2] , one of our long-standing goals has been to provide a unified model for atomic resolution protein interfaces. We took our Voronoi based modeling approach one step further, by developing a parametric model of protein binding patches, amenable to structure comparison [16] , [21] . This model may be seen as a parametric core-rim model refining the classical binary core-rim model. It encompasses both geometric and topological properties, and allows the investigation of the topology of binding patches—a dimension ignored so far. Moreover, the topological information also makes the model amenable to structure comparison, a topic hardly touched at the atomic level—the problem is in fact NP-hard. This model is currently being used to perform a detailed analysis of antibody - antigen complexes, in the perspective of understanding the relationship between the amino-acid variability of immunoglobulins, and their binding affinity.

Second, a recent achievement has been the design of an algorithm to compute so-called compoundly-weighted Voronoi diagram, in the context of TOleranced Models [5] . Recall that the TOM framework is meant to accommodate uncertainties on the shapes and the positions of proteins within large protein assemblies. In 2011, we fully exploited the TOM framework to perform analysis on qualitative reconstructions of the Nuclear Pore Complex (NPC) [20] , [19] , the largest protein assembly known to date in the eukaryotic cell [22] . This work was carried out in collaboration with V. Doye, from Inst. Jacques Monod, Paris, a renowned expert of the NPC.

We believe that the TOM framework and the accompanying statistics should prove of general interest for the problem of reconstructing macro-molecular assemblies and that of assessing such reconstructions.