Interface Dynamics In Hub Proteins

Abstract

Dynamical properties of proteins may have a significant role in regulating protein-protein interactions. In particular, intrinsic disorder and disorder-order transitions have been claimed to be especially involved in the binding of proteins known as “hubs” [1], which are characterized by a high level of connectivity in protein-protein interaction (PPI) networks. We therefore started to investigate the dynamical properties of hubs through molecular simulations, to assess the role of conformational flexibility in promoting “promiscuity” of interactions.For this study, a dataset of proteins with known structure and interaction partners was first prepared. To cope with the incompleteness of the interaction data contained in the Protein Data Bank (PDB), we mapped the PPI database IntAct [2], which collects interactions from a wide range of experimental techniques, onto the structure-based database PiSite [3]. The proteins were then partitioned into ‘classes’ with increasing number of interactions.A preliminary survey of the dynamical properties of each class was done using two independent approaches, namely tCONCOORD [4] and the Gaussian Network Model [5]. For each complex, the interfaces were extracted using the POPSComp method [6,7]. The availability of information on both the dynamics and the interaction properties will allow to determine possible correlations between flexibility and binding diversity.[1] Dosztnyi et al., J. Proteome Res., 5, 2985-2995 (2006).[2] Kerrien et al., Nucleic Acids Res., 35, D561-D565 (2006).[3] Higurashi et al., Nucleic Acids Res., 37, D360-D364 (2009).[4] Seeliger et al., Structure, 15, 1482-1492 (2007).[5] Bahar et al., Folding & Design, 2, 173-181 (1997).[6] Fraternali et al., Nucleic Acids Res., 30, 2950-2960 (2002).[7] Kleinjung et al., Nucleic Acids Res., 33, W342-W346 (2005).