title: Specificity of broad protein interaction surfaces for proteins with multiple binding partners.
abstract: Analysis of protein-protein interaction networks has revealed the presence of proteins with multiple interaction ligand proteins, such as hub proteins. For such proteins, multiple ligands would be predicted as interacting partners when predicting all-to-all protein-protein interactions (PPIs). In this work, to obtain a better understanding of PPI mechanisms, we focused on protein interaction surfaces, which differ between protein pairs. We then performed rigid-body docking to obtain information of interfaces of a set of decoy structures, which include many possible interaction surfaces between a certain protein pair. Then, we investigated the specificity of sets of decoy interactions between true binding partners in each case of alpha-chymotrypsin, actin, and cyclin-dependent kinase 2 as test proteins having multiple true binding partners. To observe differences in interaction surfaces of docking decoys, we introduced broad interaction profiles (BIPs), generated by assembling interaction profiles of decoys for each protein pair. After cluster analysis, the specificity of BIPs of true binding partners was observed for each receptor. We used two types of BIPs: those involved in amino acid sequences (BIP-seqs) and those involved in the compositions of interacting amino acid residue pairs (BIP-AAs). The specificity of a BIP was defined as the number of group members including all true binding partners. We found that BIP-AA cases were more specific than BIP-seq cases. These results indicated that the composition of interacting amino acid residue pairs was sufficient for determining the properties of protein interaction surfaces.
authors.affiliation: Department of Physics, Faculty of Science and Engineering, Chuo University, Bunkyo-ku, Tokyo 112-8551, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Uchikoga
authors.affiliation: Education Academy of Computational Life Sciences, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Computer Science, Graduate School of Information Science and Engineering, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ohue
authors.affiliation: Education Academy of Computational Life Sciences, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan; Department of Computer Science, Graduate School of Information Science and Engineering, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Akiyama
keywords: hub protein; interaction profile; postdocking process; protein-protein interaction; rigid-body docking process