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Title: xMDFF: molecular dynamics flexible fitting of low-resolution X-ray structures

A new real-space refinement method for low-resolution X-ray crystallography is presented. The method is based on the molecular dynamics flexible fitting protocol targeted at addressing large-scale deformations of the search model to achieve refinement with minimal manual intervention. An explanation of the method is provided, augmented by results from the refinement of both synthetic and experimental low-resolution data, including an independent electrophysiological verification of the xMDFF-refined crystal structure of a voltage-sensor protein. 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,more » xMDFF refinements together with electrophysiology experiments were used to validate the first all-atom structure of the voltage-sensing protein Ci-VSP.« less
Authors:
;  [1] ;  [2] ; ;  [3] ;  [2] ;  [1] ;  [4]
  1. University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States)
  2. The University of Chicago, Chicago, IL 60637 (United States)
  3. University of Missouri, Columbia, MO 65211 (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22347748
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 70; Journal Issue: Pt 9; Other Information: PMCID: PMC4157446; PMID: 25195748; PUBLISHER-ID: rr5069; OAI: oai:pubmedcentral.nih.gov:4157446; Copyright (c) Li et al. 2014; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; ATOMS; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; CRYSTALS; DEFORMATION; DENSITY; DIFFRACTION; ELECTRIC POTENTIAL; ELECTRON DENSITY; ELECTRONS; PROTEIN STRUCTURE; RESOLUTION; SENSORS; VERIFICATION