 Single isomorphous replacement

Single isomorphous replacement estimates phases in X-ray crystallography by comparing a native crystal with one heavy-atom derivative. Under the ideal crystal isomorphism assumption, a reflection's derivative structure factor is $F_{PH}=F_P+F_H$, where the heavy-atom model supplies the complex reference $F_H$. The measured magnitudes constrain $F_P$ to two circles in the complex plane: one centered at zero with radius $|F_P|$, the other centered at $-F_H$ with radius $|F_{PH}|$. A general intersection gives two phase choices.^[ref]

An original exact example uses $|F_P|=5$, $F_H=3$ real and positive, and $|F_{PH}|=\sqrt{58}$. Writing $F_P=x+iy$ givesSubtracting the equations gives $6x+9=33$, hence $x=4$ and $y=\pm 3$. The alternatives areBoth alternatives predict exactly the same native and derivative intensities. Greater precision in these two magnitudes alone cannot select between them. The phase is the missing direction of a complex amplitude, not an unmeasured additive intensity.

Multiple isomorphous replacement can supply an additional circle from another derivative. The numerical example there resolves these particular candidates. In actual measurements, uncertainty, imperfect crystal isomorphism and an imperfect heavy-atom model broaden the constraints, so exact circle crossings are an explanatory idealization.