Due to the uncertainty principle, it is not possible to precisely measure both the momentum and position of a particle simultaneously. Yet, this missing information is essential to write an equation that will ultimately determine a protein’s structure. In crystallography, this is known as the ‘phase problem’ since the inevitably missing component of diffraction data is the phase of the X-ray. Many creative solutions to this problem have been invented. One is to create a derivative protein that has a heavy atom like gold or zinc bonded to it. The heavy atom offsets nearby phases, and because it has a large number of electrons, it easily stands out within the dataset. Once the heavy atom is located, its contribution to phasing can be compared to the same location in the original sample, and the previously missing phase data can be inferred. When two or more heavy atom derivatives are used, their phases can be used to triangulate the phases of the original sample.
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“Isomorphous Replacement,” Doug Bosley, accessed August 9, 2020, https://www.dougbosley.com/items/show/10.