title: xMDFF: molecular dynamics flexible fitting of low-resolution X-ray structures.
abstract: X-ray crystallography remains the most dominant method for solving atomic structures. However, for relatively large systems, the availability of only medium-to-low-resolution diffraction data often limits the determination of all-atom details. A new molecular dynamics flexible fitting (MDFF)-based approach, xMDFF, for determining structures from such low-resolution crystallographic data is reported. xMDFF employs a real-space refinement scheme that flexibly fits atomic models into an iteratively updating electron-density map. It addresses significant large-scale deformations of the initial model to fit the low-resolution density, as tested with synthetic low-resolution maps of D-ribose-binding protein. xMDFF has been successfully applied to re-refine six low-resolution protein structures of varying sizes that had already been submitted to the Protein Data Bank. Finally, via systematic refinement of a series of data from 3.6 to 7 Å resolution, xMDFF refinements together with electrophysiology experiments were used to validate the first all-atom structure of the voltage-sensing protein Ci-VSP.
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: McGreevy
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Singharoy
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Qufei
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Computer Science, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jingfen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Computer Science, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D030562:Databases, Protein; D029968:Escherichia coli Proteins / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D033902:Periplasmic Binding Proteins / Q000737:chemistry
chemical_list: D029968:Escherichia coli Proteins; D033902:Periplasmic Binding Proteins; C028003:RbsB protein, E coli
keywords: molecular dynamics flexible fitting; xMDFF