Structural Biology

Better Models for the Crystals of Biological Macromolecules

In crystallography, the R-value reports on how well a model agrees with the experimental data. In small molecule crystallography, R-values of 3% are routinely reached. However, for biological macromolecules, R-values are usually around 20%. Something is amiss; our current models of macromolecular crystal structures are incomplete, partially incorrect, or the data have errors that we are not accounting for. These shortcomings particularly impede the determination of challenging structures, such as membrane proteins, where often only low resolution data are available. In these cases, the poor phase estimates currently obtainable result in noisy electron density maps that are difficult or even impossible to interpret. In collaboration with Armin Wagner's group at Diamond Lightsource, we try to shed light on these problems and improve our molecular models of biological crystals, so that we cannot only solve borderline cases but also improve all known structures.

Left: Crystallographic map (blue mesh); poor phases dominate the map and it has several problems (arrows) that make it difficult to interpret. The model (sticks) is shown for clarity. Right: An ideal map would be much easier to interpret.

These deficits become even more pronounced when compared to maps from cryo-EM where the phases are determined directly from the experimental data (see Fig.).

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