Model-building strategies for low-resolution X-ray crystallographic data

The interpretation of low-resolution X-ray crystallographic data proves to be challenging even for the most experienced crystallographer. Ambiguity in the electron-density map makes main-chain tracing and side-chain assignment difficult. However, the number of structures solved at resolutions poorer than 3.5 Å is growing rapidly and the structures are often of high biological interest and importance. Here, the challenges faced in electron-density interpretation, the strategies that have been employed to overcome them and developments to automate the process are reviewed. The methods employed in model generation from electron microscopy, which share many of the same challenges in providing high-confidence models of macromolecular structures and assemblies, are also considered.