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.

Exploring the Protein G Helix Free Energy Surface by Solute Tempering Metadynamics / C. Camilloni, D. Provasi, G. Tiana, R. A. Broglia. - In: PROTEINS. - ISSN 0887-3585. - 71:4(2008), pp. 1647-1654.

Exploring the Protein G Helix Free Energy Surface by Solute Tempering Metadynamics

C. Camilloni
Primo
;
D. Provasi
Secondo
;
G. Tiana
Penultimo
;
R. A. Broglia
Ultimo
2008

Abstract

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.
Settore FIS/03 - Fisica della Materia
Settore FIS/04 - Fisica Nucleare e Subnucleare
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/35756
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