title: Effect of external pulling forces on the length distribution of peptides.
abstract: BACKGROUND
  The distribution of the length of a polypeptide, or that of the distance between any two of its atoms, is an important property as it can be analytically or numerically estimated for a number of polymer models. Importantly, it is directly measurable through a number of different experimental techniques. Length distributions can be straightforwardly assessed from molecular dynamics simulation; however, true convergence through full accurate coverage of the length range is difficult to achieve.
  
  
  METHODS
  The application of external constant force combined with the weighted-histogram analysis method (WHAM) is used to enhance sampling of unlikely 'long' or 'short' conformations and obtain the potential of mean force, while also collecting dynamic properties of the chain under variable tension.
  
  
  RESULTS
  We demonstrate the utility of constant force to enhance the sampling efficiency and obtain experimentally measurable quantities on a series of short peptides, including charge-rich sequences that are known to be highly helical but whose properties are distinct from those of helical peptides undergoing helix-coil transitions.
  
  
  CONCLUSIONS
  Force-enhanced sampling enhances the range and accuracy of the length-based potential of mean force of the peptide, in particular those sequences that contain increased numbers of charged residues.
  
  
  CONCLUSIONS
  This approach allows users to simultaneously probe the force-dependent behaviour of peptides directly, enhance the range and accuracy of the length-based PMF of the peptide and also test the convergence of simulations by comparing the overlap of PMF profiles from different constant forces. This article is part of a special issue entitled Recent developments of molecular dynamics.
authors.affiliation: School of Molecular and Cellular Biology and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Batchelor
authors.affiliation: School of Molecular and Cellular Biology and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: James
authors.initials: J
authors.lastname: Gowdy
authors.affiliation: School of Molecular and Cellular Biology and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. Electronic address: e.paci@leeds.ac.uk.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Paci
mesh_terms: D001120:Arginine / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D009842:Oligopeptides; D018698:Glutamic Acid; D001120:Arginine; D008239:Lysine; D005998:Glycine
keywords: Alpha helix; Force; Freely jointed chain; Length distribution; Peptides; Random coil