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interrogating fragment libraries by x - ray crystallography is a powerful strategy for discovering allosteric ligands for protein targets . 
 cryocooling of crystals should theoretically increase the fraction of occupied binding sites and decrease radiation damage . 
 however , it might also perturb protein conformations that can be accessed at room temperature . using data from crystals measured consecutively at room temperature and at cryogenic temperature 
 , we found that transient binding sites could be abolished at the cryogenic temperatures employed by standard approaches . 
 changing the temperature at which the crystallographic data was collected could provide a deliberate perturbation to the equilibrium of protein conformations and help to visualize hidden sites with great potential to allosterically modulate protein function .