articleProceedings of the National Academy of SciencesSep 14, 2011Closed access

Accessing protein conformational ensembles using room-temperature X-ray crystallography

University of California, Berkeley · SLAC National Accelerator Laboratory · +4 more institutions

PubMed
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Abstract

Modern protein crystal structures are based nearly exclusively on X-ray data collected at cryogenic temperatures (generally 100 K). The cooling process is thought to introduce little bias in the functional interpretation of structural results, because cryogenic temperatures minimally perturb the overall protein backbone fold. In contrast, here we show that flash cooling biases previously hidden structural ensembles in protein crystals. By analyzing available data for 30 different proteins using new computational tools for electron-density sampling, model refinement, and molecular packing analysis, we found that crystal cryocooling remodels the conformational distributions of more than 35% of side chains and…

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