Linking well-tempered metadynamics simulations with experiments.
Linking experiments with the atomistic resolution provided by molecular dynamics simulations can shed light on the structure and dynamics of protein-disordered states. The sampling limitations of classical molecular dynamics can be overcome using metadynamics, which is based on the introduction of a history-dependent bias on a small number of suitably chosen collective variables. Even if such bias distorts the probability distribution of the other degrees of freedom, the equilibrium Boltzmann distribution can be reconstructed using a recently developed reweighting algorithm. Quantitative comparison with experimental data is thus possible. Here we show the potential of this combined approach by characterizing the conformational ensemble explored by a 13-residue helix-forming peptide by means of a well-tempered metadynamics/parallel tempering approach and comparing the reconstructed nuclear magnetic resonance scalar couplings with experimental data.
Barducci
Alessandro
A
Computational Science, Department of Chemistry and Applied Biosciences, ETH Zurich, USI Campus, Lugano, Switzerland. alessandro.barducci@phys.chem.ethz.ch
Bonomi
Massimiliano
M
Parrinello
Michele
M
D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry; D011487:Protein Conformation; D015203:Reproducibility of Results; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D013816:Thermodynamics
D010446:Peptide Fragments; D012259:Ribonuclease, Pancreatic