Open AccessxMDFF: molecular dynamics flexible fitting of low‐resolution X‐ray structures
Author(s) -
McGreevy Ryan,
Singharoy Abhishek,
Li Qufei,
Zhang Jingfen,
Xu Dong,
Perozo Eduardo,
Schulten Klaus
Publication year - 2014
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s1399004714013856
Subject(s) - resolution (logic) , low resolution , series (stratigraphy) , algorithm , molecular dynamics , diffraction , atom (system on chip) , computer science , biological system , crystallography , high resolution , computational physics , chemistry , physics , computational chemistry , artificial intelligence , optics , biology , paleontology , remote sensing , embedded system , geology
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.