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Section: New Results

Modeling Interfaces and Contacts

On the Morphology of Protein Binding Patches

Participants : Frédéric Cazals, Noël Malod-Dognin.

In collaboration with A. Bansal, former summer intern from IIT Bombay.

Understanding the specificity of protein interactions is a central question in structural biology, whence the importance of models for protein binding patches—a patch refers to the collection of atoms of a given partner accounting for the interaction. To improve our understanding of the relationship between the structure of binding patches and the biological function of protein complexes, we present a binding patch model decoupling the topological and geometric properties [21] . While the geometry is classically encoded by the 3D positions of the atoms, the topology is recorded in a graph encoding the relative position of concentric shells partitioning the interface atoms. The topological - geometric duality provides the basis of a generic dynamic programming based algorithm to compare patches, which is instantiated to respectively favor topological or geometric comparisons.

On the biological side, using a dataset of 92 co-crystallized structures organized in biological sub-families, we exploit our encoding and the two comparison algorithms in two directions. First, we show that Nature enjoyed the topological and geometric degrees of freedom independently while retaining a finite set of qualitatively distinct topological signatures, and show that topological similarity is a less stringent notion that the ubiquitously used geometric similarity. Second, we analyze the topological and geometric coherence of binding patches within sub-families and across the whole database, and show that complexes related to the same biological function can encompass geometrically distinct shapes. Previous work on binding patches focused on the investigation of correlations between structural parameters and biochemical properties on the one hand, and on structural comparison algorithms on the other hand. We believe that the abstraction coded by the topological - geometric duality paves the way to new classifications, in particular in the context of flexible docking.

The corresponding software is presented in section 5.1.1 .