Improvement of search models against the experimental data, relying on PHASER’s rotation function and SHELXE pdb optimization
Molecular replacement relies on the availability of suitable models to be placed in the unit cell of the unknown structure in order to provide initial phases. ARCIMBOLDO, originally conceived for ab initio phasing, operates at the limit of this approach, using small, very accurate fragments such as polyalanine alpha-helices. A distant homolog may contain such accurate building blocks, while it may not be evident which substructure will be most suitable purely from the degree of conservation.
ARCIMBOLDO-SHREDDER exploits fragments from distant homologs to phase macromolecular structures. In this strategy, the initial template is systematically shredded and fragments are scored against each unique solution of the rotation function. Results are combined into a score per residue and the template is trimmed accordingly. Models are selected by optimization of PHASER’s rotation function and of the SHELXE correlation coefficient trimming the positioned substructure.