TOOLS TO AID MACROMOLECULAR REFINEMENT AT LOW RESOLUTION

Regularisers stabilise macromolecular refinement, ensuring consistency between derived models and prior knowledge. Restraints representing chemical information help local structure adopt chemically reasonable conformations. At lower resolutions, supplementary restraints are used: encouraging consistency with models of homologous structures, formation of hydrogen bonding networks, nucleotide base pairing and stacking. Jelly-body restraints stabilise model refinement without injecting externally derived information. An anharmonic penalty function is used in order to control robustness to outliers due to inconsistencies between data and prior. Additional restraints and robust estimation are also useful for model building, increasing real space refinement convergence radius and stability.