************ Introduction ************ 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. How to cite use of Grade2 ========================= Please see the :ref:`FAQ on citing `. Getting help on Grade2 ====================== Please see the :ref:`FAQ on problems with Grade2 and help `.