What is Grade2?¶
Grade2 is a tool for generating restraint dictionaries for ligands in macromolecular structure determination. Such a dictionary provides stereochemical restraints that are essential to produce chemically reasonable structures in X-ray refinement of macromolecules in normal resolution ranges (Steiner and Tucker, 2017). A restraint dictionary describes the conformational flexibility of the ligand molecule, and so is essential for ligand fitting into electron density (both manually using Coot (Emsley and Cowtan, 2004) or with automated ligand fitting tools such as Rhofit).
Grade2 is distributed as part of the BUSTER package https://www.globalphasing.com/buster/ but its restraint dictionaries can be used by a wide range of building, fitting and refinement tools. Grade2 is a reimplementation of the original Grade restraint generation tool that was developed at Global Phasing from 2010. Grade2 (like Grade) aims to produce restraints using information from the Cambridge Structural Database (CSD) of small-molecule organic crystal structures whenever possible. Both Grade and Grade2 use the Mogul tool (Bruno et al., 2004) to search the CSD. But whereas Grade uses the Mogul program in batch mode via a Mogul Instruction File, Grade2 performs Mogul search with the CSD Python API, allowing additional custom analysis. Where CSD information is not available Grade and Grade2 base restraints on computational chemistry methods. Currently, Grade2 uses the MMFF94s (Halgren, 1996) or UFF force field (Rappe et al., 1992) as implemented (Tosco et al., 2014) in the RDKit package.