Premium
Real‐space refinement with DireX: From global fitting to side‐chain improvements
Author(s) -
Wang Zhe,
Schröder Gunnar F.
Publication year - 2012
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22046
Subject(s) - overfitting , resolution (logic) , range (aeronautics) , cryo electron microscopy , computer science , low resolution , degrees of freedom (physics and chemistry) , algorithm , chemistry , biological system , high resolution , artificial intelligence , physics , aerospace engineering , artificial neural network , thermodynamics , biochemistry , remote sensing , geology , biology , engineering
Single‐particle cryo‐electron microscopy (cryo‐EM) has become an important tool to determine the structure of large biomolecules and assemblies thereof. However, the achievable resolution varies considerably over a wide range of about 3.5–20 Å. The interpretation of these intermediate‐ to low‐resolution density maps in terms of atomic models is a big challenge and an area of active research. Here, we present our real‐space structure refinement program DireX, which was developed primarily for cryo‐EM‐derived density maps. The basic principle and its main features are described. DireX employs Deformable Elastic Network (DEN) restraints to reduce overfitting by decreasing the effective number of degrees of freedom used in the refinement. Missing or reduced density due to flexible parts of the protein can lead to artifacts in the structure refinement, which is addressed through the concept of restrained grouped occupancy refinement. Furthermore, we describe the performance of DireX in the 2010 Cryo‐EM Modeling Challenge, where we chose six density maps of four different proteins provided by the Modeling Challenge exemplifying typical refinement results at a large resolution range from 3 to 23 Å. © 2012 Wiley Periodicals, Inc. Biopolymers 97: 687–697, 2012.