De novo protein structure determination using single isomorphous replacement (SIR) or single wavelength anomalous diffraction (SAD) data is important when it is difficult to prepare multiple isomorphous derivatives and to collect multiwavelength anomalous diffraction (MAD) data. However the phase ambiguity intrinsic in SIR/SAD data obstructs the use of them. The combination of direct methods with SIR or SAD technique may solve the problem and simplify the process of structure determination.
        MAD and MIR are two major methods of de novo solution of protein structures. The incorporation of direct methods with MAD or MIR phasing may lead to better results.
        Direct methods are also useful in the dual-space fragment extension with or without SAD/SIR information.