Cross-crystal averaging with search models to improve molecular replacement phases

Weikai Li, Fang Li

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The application of molecular replacement (MR) in macromolecular crystallography can be limited by the "model bias" problem. Here we propose a strategy to reduce model bias when only part of a new structure is known: after the MR search, structure determination of the unknown part of the new structure can be facilitated by cross-crystal averaging of the known part of the new structure with the search model. This strategy dramatically improves electron density in the unknown part of the new structure. It has enabled us to determine the structures of two coronavirus receptor-binding domains each complexed with their receptor at moderate resolutions. In a test case, it also enabled automated model building when >50% of an antigen-antibody complex was absent. These results suggest that this averaging strategy can be routinely used after MR to enhance the interpretability of electron density associated with missing model.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalStructure
Volume19
Issue number2
DOIs
StatePublished - Feb 9 2011

Bibliographical note

Funding Information:
We thank Dr. Carrie Wilmot, Dr. Yuhong Jiang, and Dr. Yong Xiong for discussion and comments. This work was supported by the National Heart, Lung, and Blood Institute (K99HL097083 to W.L.), the National Institute of Allergy and Infectious Diseases (R01AI089728 to F.L.), and a University of Minnesota AHC Faculty Research Development Grant (to F.L.). Computer resources were provided by the Basic Sciences Computing Laboratory of the University of Minnesota Supercomputing Institute.

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