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Improved crystallographic models through iterated local density-guided model deformation and reciprocal-space refinement.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Terwilliger, Thomas C 
Read, Randy J 
Adams, Paul D 
Brunger, Axel T 
Afonine, Pavel V 

Abstract

An approach is presented for addressing the challenge of model rebuilding after molecular replacement in cases where the placed template is very different from the structure to be determined. The approach takes advantage of the observation that a template and target structure may have local structures that can be superimposed much more closely than can their complete structures. A density-guided procedure for deformation of a properly placed template is introduced. A shift in the coordinates of each residue in the structure is calculated based on optimizing the match of model density within a 6 Å radius of the center of that residue with a prime-and-switch electron-density map. The shifts are smoothed and applied to the atoms in each residue, leading to local deformation of the template that improves the match of map and model. The model is then refined to improve the geometry and the fit of model to the structure-factor data. A new map is then calculated and the process is repeated until convergence. The procedure can extend the routine applicability of automated molecular replacement, model building and refinement to search models with over 2 Å r.m.s.d. representing 65-100% of the structure.

Description

Keywords

Acetylesterase, Crystallography, X-Ray, Models, Molecular, Protein Conformation, Ruminococcus

Journal Title

Acta Crystallogr D Biol Crystallogr

Conference Name

Journal ISSN

0907-4449
1399-0047

Volume Title

68

Publisher

International Union of Crystallography (IUCr)

Rights

All rights reserved
Sponsorship
Wellcome Trust (082961/Z/07/Z)
National Institute of General Medical Sciences (P01GM063210)