title: Biomolecular structure refinement based on adaptive restraints using local-elevation simulation.
abstract: Introducing experimental values as restraints into molecular dynamics (MD) simulation to bias the values of particular molecular properties, such as nuclear Overhauser effect intensities or distances, dipolar couplings, 3 J-coupling constants, chemical shifts or crystallographic structure factors, towards experimental values is a widely used structure refinement method. Because multiple torsion angle values varphi correspond to the same 3 J-coupling constant and high-energy barriers are separating those, restraining 3 J-coupling constants remains difficult. A method to adaptively enforce restraints using a local elevation (LE) potential energy function is presented and applied to 3 J-coupling constant restraining in an MD simulation of hen egg-white lysozyme (HEWL). The method succesfully enhances sampling of the restrained torsion angles until the 37 experimental 3 J-coupling constant values are reached, thereby also improving the agreement with the 1,630 experimental NOE atom-atom distance upper bounds. Afterwards the torsional angles varphi are kept restrained by the built-up local-elevation potential energies.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zürich, ETH-Zürich, 8093 Zürich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Christen
authors.forename: Bettina
authors.initials: B
authors.lastname: Keller
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D000818:Animals; D003198:Computer Simulation; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D011487:Protein Conformation
chemical_list: C421864:hen egg lysozyme; D009113:Muramidase