title: Exploring the protein G helix free-energy surface by solute tempering metadynamics.
abstract: The free-energy landscape of the alpha-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 beta-structure, that the helical state is metastable and involves only 65% of the chain. The calculations also show that the system populates consistently a pi-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.
authors: Department of Physics, University of Milano, via Celoria 16, Milan 20133, Italy.
authors: Carlo
authors: C
authors: Camilloni
authors: Davide
authors: D
authors: Provasi
authors: Guido
authors: G
authors: Tiana
authors: Ricardo A
authors: RA
authors: Broglia
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D003198:Computer Simulation; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: C029152:G-substrate; D009419:Nerve Tissue Proteins; D012997:Solvents; D014867:Water