ModelCraft: an advanced automated model-building pipeline using Buccaneer

Abstract

Interactive model building can be a difficult and time-consuming step in the structure-solution process. Automated model-building programs such as Buccaneer often make it quicker and easier by completing most of the model in advance. However, they may fail to do so with low-resolution data or a poor initial model or map. The Buccaneer pipeline is a relatively simple program that iterates Buccaneer with REFMAC to refine the model and update the map. A new pipeline called ModelCraft has been developed that expands on this to include shift-field refinement, machine-learned pruning of incorrect residues, classical density modification, addition of water and dummy atoms, building of nucleic acids and final rebuilding of side chains. Testing was performed on 1180 structures solved by experimental phasing, 1338 structures solved by molecular replacement using homologues and 2030 structures solved by molecular replacement using predicted AlphaFold models. Compared with the previous Buccaneer pipeline, ModelCraft increased the mean completeness of the protein models in the experimental phasing cases from 91% to 95%, the molecular-replacement cases from 50% to 78% and the AlphaFold cases from 82% to 91%.

Identification of a novel 5-aminomethyl-2-thiouridine methyltransferase in tRNA modification

“…To solve the phase problem, molecular replacement was performed using the SAM-bound bs YtqB structure (PDB: 4POO) as a search model using MOLREP ( 58 ). Initial model building was enabled by ModelCraft ( 59 ) and PDB_REDO server ( 60 ). The final model was polished by iterative cycles of real space model building using Coot ( 61 ) and refinement by REFMAC5 ( 62 ) and Phenix.refine ( 63 ).…”

The yeast ALA synthase C‐terminus positively controls enzyme structure and function

“…Molecular replacement was performed in PHASER (McCoy et al, 2007) using one subunit of wildtype Hem1 (PDB 5TXR) as the search model, yielding a single unique solution containing two molecules (one biological homodimer) in the asymmetric unit. Automatic model building and initial refinement were done with ModelCraft (Bond & Cowtan, 2022). Rounds of iterative model building and refinement were performed using Coot and REFMAC5 in the CCP4 program suite (Emsley et al, 2010; Murshudov et al, 2011; Winn et al, 2011).…”

The CCP4 suite: integrative software for macromolecular crystallography

“…It is based on a novel approach in which a shift field, and not atoms, is refined to update and morph models. This approach is particularly indicated to correct large shifts in secondary-structure elements after molecular replacement and is run by default as part of the Modelcraft pipeline (Bond & Cowtan, 2022).…”