Model building, refinement and validation

The CCP4 Study Weekend 2011 was held at the University of Warwick on the 6–7 January. Following a long established tradition of discussing at the Study Weekend the most important crystallographic topics, the choice for 2011 was the 'Model building, refinement and validation' triple bill. As a result of the extraordinary efforts of instrumentation and software developers, macromolecular crystallography has been greatly automated to a point where it can be treated as a black-box method with little input required by the user. This is not without danger. The complexity and size of problems tackled has kept pace with the developments , and competent work still requires a great deal of knowledge about the methods and, naturally, about the source of the remaining challenges. In the process of structure solution, model building is often a very satisfying step in which the scientist acquaints him/herself with the macromolecule(s) under study and biological hypotheses start taking shape. It is however not without hurdles and potential pitfalls, particularly when only data at limited resolution are available. The best possible electron-density maps which guide further model (re)building and afford additional biological insight are calculated as part of crystallographic refinement. In this step one maximizes the agreement between the X-ray data and our (atomistic) interpretation of the diffraction experiment. Although the stereochemical restraints employed during the crystallographic refinement try to maintain a chemically sound model, constant and concurrent validation is required. Robust and easily accessible tools for global and local quality analyses are critical to ensure that reliable structures are made available to the scientific community at large. The Study Weekend 2011 was opened with a talk by Bernhard Rupp who provided an overview of the key challenges that are still present in the field of macromolecular crystallography with a particular focus on the three main topics of the meeting. The challenges originate from two major sources. On one hand there are difficulties resulting from the complex nature of the biomacromolecules self-assembling into an imperfect crystal (such as dynamic motion, disorder, limited diffraction, twinning and lattice modulation). On the other hand there are fundamental problems inherent in a highly multivariate parameter space with an often barely sufficient data-to-parameter ratio. Bernhard's talk was followed by one by George Sheldrick. George further developed the general themes outlined in the previous talk and described in more detail the foundations of crystallographic refinement emphasising the importance of proper restraints. After …