FALCON@home: a high-throughput protein structure prediction server based on remote homologue recognition

Bioinformatics. 2016 Feb 1;32(3):462-4. doi: 10.1093/bioinformatics/btv581. Epub 2015 Oct 10.

Abstract

Summary: The protein structure prediction approaches can be categorized into template-based modeling (including homology modeling and threading) and free modeling. However, the existing threading tools perform poorly on remote homologous proteins. Thus, improving fold recognition for remote homologous proteins remains a challenge. Besides, the proteome-wide structure prediction poses another challenge of increasing prediction throughput. In this study, we presented FALCON@home as a protein structure prediction server focusing on remote homologue identification. The design of FALCON@home is based on the observation that a structural template, especially for remote homologous proteins, consists of conserved regions interweaved with highly variable regions. The highly variable regions lead to vague alignments in threading approaches. Thus, FALCON@home first extracts conserved regions from each template and then aligns a query protein with conserved regions only rather than the full-length template directly. This helps avoid the vague alignments rooted in highly variable regions, improving remote homologue identification. We implemented FALCON@home using the Berkeley Open Infrastructure of Network Computing (BOINC) volunteer computing protocol. With computation power donated from over 20,000 volunteer CPUs, FALCON@home shows a throughput as high as processing of over 1000 proteins per day. In the Critical Assessment of protein Structure Prediction (CASP11), the FALCON@home-based prediction was ranked the 12th in the template-based modeling category. As an application, the structures of 880 mouse mitochondria proteins were predicted, which revealed the significant correlation between protein half-lives and protein structural factors.

Availability and implementation: FALCON@home is freely available at http://protein.ict.ac.cn/FALCON/.

Contact: shuaicli@cityu.edu.hk, dbu@ict.ac.cn

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Animals
  • Computational Biology / methods
  • Databases, Protein
  • High-Throughput Screening Assays
  • Mice
  • Protein Conformation*
  • Proteins / chemistry*
  • Sequence Alignment / methods*
  • Sequence Analysis, Protein / methods*
  • Software*

Substances

  • Proteins