Identification of hot regions in protein-protein interactions by sequential pattern mining.
BACKGROUND
Identification of protein interacting sites is an important task in computational molecular biology. As more and more protein sequences are deposited without available structural information, it is strongly desirable to predict protein binding regions by their sequences alone. This paper presents a pattern mining approach to tackle this problem. It is observed that a functional region of protein structures usually consists of several peptide segments linked with large wildcard regions. Thus, the proposed mining technology considers large irregular gaps when growing patterns, in order to find the residues that are simultaneously conserved but largely separated on the sequences. A derived pattern is called a cluster-like pattern since the discovered conserved residues are always grouped into several blocks, which each corresponds to a local conserved region on the protein sequence.


RESULTS
The experiments conducted in this work demonstrate that the derived long patterns automatically discover the important residues that form one or several hot regions of protein-protein interactions. The methodology is evaluated by conducting experiments on the web server MAGIIC-PRO based on a well known benchmark containing 220 protein chains from 72 distinct complexes. Among the tested 218 proteins, there are 900 sequential blocks discovered, 4.25 blocks per protein chain on average. About 92% of the derived blocks are observed to be clustered in space with at least one of the other blocks, and about 66% of the blocks are found to be near the interface of protein-protein interactions. It is summarized that for about 83% of the tested proteins, at least two interacting blocks can be discovered by this approach.


CONCLUSIONS
This work aims to demonstrate that the important residues associated with the interface of protein-protein interactions may be automatically discovered by sequential pattern mining. The detected regions possess high conservation and thus are considered as the computational hot regions. This information would be useful to characterizing protein sequences, predicting protein function, finding potential partners, and facilitating protein docking for drug discovery.
Hsu
Chen-Ming
CM
Department of Computer Science and Engineering, Yuan Ze University, Chung-Li, Taiwan, ROC. cmhsu@saturn.yzu.edu.tw
Chen
Chien-Yu
CY
Liu
Baw-Jhiune
BJ
Huang
Chih-Chang
CC
Laio
Min-Hung
MH
Lin
Chien-Chieh
CC
Wu
Tzung-Lin
TL
D001426:Bacterial Proteins / Q000737:chemistry; D043422:Carboxypeptidases A / Q000737:chemistry; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry; D008954:Models, Biological; D025941:Protein Interaction Mapping / Q000379:methods*; D020744:rac GTP-Binding Proteins / Q000737:chemistry; D020703:ras GTPase-Activating Proteins / Q000737:chemistry; D000097766:RAC2 GTP-Binding Protein
D001426:Bacterial Proteins; D043422:Carboxypeptidases A; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D006360:Heat-Shock Proteins; D020744:rac GTP-Binding Proteins; D020703:ras GTPase-Activating Proteins; D000097766:RAC2 GTP-Binding Protein; C068113:GrpE protein, Bacteria