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Journal of Statistical Physics

, Volume 162, Issue 5, pp 1267–1293 | Cite as

On the Entropy of Protein Families

  • John P. Barton
  • Arup K. Chakraborty
  • Simona Cocco
  • Hugo Jacquin
  • Rémi Monasson
Article

Abstract

Proteins are essential components of living systems, capable of performing a huge variety of tasks at the molecular level, such as recognition, signalling, copy, transport, ... The protein sequences realizing a given function may largely vary across organisms, giving rise to a protein family. Here, we estimate the entropy of those families based on different approaches, including Hidden Markov Models used for protein databases and inferred statistical models reproducing the low-order (1- and 2-point) statistics of multi-sequence alignments. We also compute the entropic cost, that is, the loss in entropy resulting from a constraint acting on the protein, such as the mutation of one particular amino-acid on a specific site, and relate this notion to the escape probability of the HIV virus. The case of lattice proteins, for which the entropy can be computed exactly, allows us to provide another illustration of the concept of cost, due to the competition of different folds. The relevance of the entropy in relation to directed evolution experiments is stressed.

Keywords

Statistical inference Entropy Fitness landscape  Genomics Hidden Markov models Covariation HIV virus 

Notes

Acknowledgments

S.C., H.J. and R.M. were partly funded by the Agence Nationale de la Recherche Coevstat project (ANR-13-BS04-0012-01).

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • John P. Barton
    • 1
    • 2
    • 3
    • 6
  • Arup K. Chakraborty
    • 1
    • 2
    • 3
    • 4
    • 5
    • 6
  • Simona Cocco
    • 7
  • Hugo Jacquin
    • 7
  • Rémi Monasson
    • 8
  1. 1.Ragon Institute of MGHMIT & HarvardCambridgeUSA
  2. 2.Department of Chemical EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  3. 3.Department of PhysicsMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Department of ChemistryMassachusetts Institute of TechnologyCambridgeUSA
  5. 5.Department of Biological EngineeringMassachusetts Institute of TechnologyCambridgeUSA
  6. 6.Institute for Medical Engineering & ScienceMassachusetts Institute of TechnologyCambridgeUSA
  7. 7.Laboratoire de Physique Statistique de l’ENSUMR 8550, associé au CNRS et à l’Université P&M. CurieParisFrance
  8. 8.Laboratoire de Physique Théorique de l’ENSUMR 8549, associé au CNRS et à l’Université P&M. CurieParisFrance

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