On the packing density of the unbound protein-protein interaction interface and its implications in dynamics

摘要

Background: Characterizing the interface residues will help shed light on protein-protein interactions, which are involved in many important biological processes. Many studies focus on characterizing seguence or structure features of protein interfaces, but there are few studies characterizing the dynamics of interfaces. Therefore, we would like to know whether there is any specific dynamics pattern in the protein-protein interaction interfaces. Thermal fluctuation is an important dynamical propertyfor a residue, and could be guickly estimated by local packing density without large computation since studies have showen closely relationship between these two properties. Therefore, we divided surface of an unbound subunit (free protein subunits before they are involved in forming the protein complexes) into several separate regions, and compared their average thermal fluctuations of different regions in order to characterize the dynamics pattern in unbound protein-protein interaction interfaces.Results: We used weighted contact numbers (WCN), a parameter-free method to guantify packing density, to estimate the thermal fluctuations of residues in the interfaces. By analyzing the WCN distributions of interfaces in unbound subunits from 1394 non-homologous protein complexes, we show that the residues in the central regions of interfaces have higher packing density (i.e. more rigid); on the other hand, residues surrounding the central regions have smaller packing density (i.e. more flexible). Thedistinct distributions of packing density, suggesting distinct thermal fluctuation, reveals specific dynamics pattern in the interface of unbound protein subunits.Conclusions: We found general trend that the unbound protein-protein interaction interfaces consist of rigid residues in the central regions, which are surrounded by flexible residues. This finding suggests that the dynamics might be one of the importantfeatures for the formation of protein complexes.