A consensus method for the prediction of 'aggregation-prone' peptides in globular proteins

PLoS One. 2013;8(1):e54175. doi: 10.1371/journal.pone.0054175. Epub 2013 Jan 10.

Abstract

The purpose of this work was to construct a consensus prediction algorithm of 'aggregation-prone' peptides in globular proteins, combining existing tools. This allows comparison of the different algorithms and the production of more objective and accurate results. Eleven (11) individual methods are combined and produce AMYLPRED2, a publicly, freely available web tool to academic users (http://biophysics.biol.uoa.gr/AMYLPRED2), for the consensus prediction of amyloidogenic determinants/'aggregation-prone' peptides in proteins, from sequence alone. The performance of AMYLPRED2 indicates that it functions better than individual aggregation-prediction algorithms, as perhaps expected. AMYLPRED2 is a useful tool for identifying amyloid-forming regions in proteins that are associated with several conformational diseases, called amyloidoses, such as Altzheimer's, Parkinson's, prion diseases and type II diabetes. It may also be useful for understanding the properties of protein folding and misfolding and for helping to the control of protein aggregation/solubility in biotechnology (recombinant proteins forming bacterial inclusion bodies) and biotherapeutics (monoclonal antibodies and biopharmaceutical proteins).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloidogenic Proteins / chemistry*
  • Databases, Protein
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Peptides / chemistry*
  • Protein Folding*
  • Software*
  • Solubility

Substances

  • Amyloidogenic Proteins
  • Peptides

Grant support

The authors thank the University of Athens for support. They also thank the Cooperation 2011 program (11SYN_1_1230) of the General Secretariat for Research and Technology of the Greek Ministry of Education and Religious Affairs, Culture and Sports, under the NSRF 2007–2013, for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.