Systems and Synthetic Biology

, Volume 4, Issue 4, pp 271–280 | Cite as

Sequence signatures of allosteric proteins towards rational design

  • Saritha Namboodiri
  • Chandra Verma
  • Pawan K. Dhar
  • Alessandro Giuliani
  • Achuthsankar S. Nair
Research Paper


Allostery is the phenomenon of changes in the structure and activity of proteins that appear as a consequence of ligand binding at sites other than the active site. Studying mechanistic basis of allostery leading to protein design with predetermined functional endpoints is an important unmet need of synthetic biology. Here, we screened the amino acid sequence landscape in search of sequence-signatures of allostery using Recurrence Quantitative Analysis (RQA) method. A characteristic vector, comprised of 10 features extracted from RQA was defined for amino acid sequences. Using Principal Component Analysis, four factors were found to be important determinants of allosteric behavior. Our sequence–based predictor method shows 82.6% accuracy, 85.7% sensitivity and 77.9% specificity with the current dataset. Further, we show that Laminarity-Mean-hydrophobicity representing repeated hydrophobic patches is the most crucial indicator of allostery. To our best knowledge this is the first report that describes sequence determinants of allostery based on hydrophobicity. As an outcome of these findings, we plan to explore possibility of inducing allostery in proteins.


Allostery Recurrence Quantitative Analysis Sequence-based predictor Hydrophobicity 



This work was funded by Kerala Government grant for the Inter University Centre for Excellence. The authors would like to thank Prof. Anders Liljas for his valuable comments.


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Saritha Namboodiri
    • 1
  • Chandra Verma
    • 2
  • Pawan K. Dhar
    • 3
  • Alessandro Giuliani
    • 4
  • Achuthsankar S. Nair
    • 1
  1. 1.State Inter University Centre of Excellence in BioinformaticsUniversity of KeralaThiruvananthapuramIndia
  2. 2.Bioinformatics Institute (BII)Buona VistaSingapore
  3. 3.Centre for Systems and Synthetic BiologyUniversity of KeralaThiruvananthapuramIndia
  4. 4.Environment and Health Deptartment, Istituto Superiore di SanitàRomeItaly

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