Format

Send to

Choose Destination
See comment in PubMed Commons below
J Struct Biol. 2012 Sep;179(3):338-46. doi: 10.1016/j.jsb.2012.02.002. Epub 2012 Feb 14.

Enriching the human apoptosis pathway by predicting the structures of protein-protein complexes.

Author information

1
Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, 34450 Sariyer Istanbul, Turkey.

Abstract

Apoptosis is a matter of life and death for cells and both inhibited and enhanced apoptosis may be involved in the pathogenesis of human diseases. The structures of protein-protein complexes in the apoptosis signaling pathway are important as the structural pathway helps in understanding the mechanism of the regulation and information transfer, and in identifying targets for drug design. Here, we aim to predict the structures toward a more informative pathway than currently available. Based on the 3D structures of complexes in the target pathway and a protein-protein interaction modeling tool which allows accurate and proteome-scale applications, we modeled the structures of 29 interactions, 21 of which were previously unknown. Next, 27 interactions which were not listed in the KEGG apoptosis pathway were predicted and subsequently validated by the experimental data in the literature. Additional interactions are also predicted. The multi-partner hub proteins are analyzed and interactions that can and cannot co-exist are identified. Overall, our results enrich the understanding of the pathway with interactions and provide structural details for the human apoptosis pathway. They also illustrate that computational modeling of protein-protein interactions on a large scale can help validate experimental data and provide accurate, structural atom-level detail of signaling pathways in the human cell.

PMID:
22349545
PMCID:
PMC3378801
DOI:
10.1016/j.jsb.2012.02.002
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center