Exploring the protein G helix free-energy surface by solute tempering metadynamics

Carlo Camilloni, Davide Provasi, Guido Tiana, Ricardo A. Broglia

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


The free-energy landscape of the tt-helix of protein G is studied by means of metadynamics coupled with a solute tempering algorithm. Metadynamics allows to overcome large energy barriers, whereas solute tempering improves the sampling with an affordable computational effort. From the sampled free-energy surface we are able to reproduce a number of experimental observations, such as the fact that the lowest minimum corresponds to a globular conformation displaying some degree of β-structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a π-helix state and that the hydrophobic staple motif is present only in the free-energy minimum associated with the helices, and contributes to their stabilization. The use of metadynamics coupled with solute tempering results then particularly suitable to provide the thermodynamics of a short peptide, and its computational efficiency is promising to deal with larger proteins.

Original languageEnglish
Pages (from-to)1647-1654
Number of pages8
JournalProteins: Structure, Function and Bioinformatics
Issue number4
StatePublished - Jun 2008
Externally publishedYes


  • Free-energy surface
  • Metadynamics
  • Protein G
  • Solute tempering
  • α-helix
  • π-helix


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