Combining direct methods with isomorphous replacement or anomalous scattering data. VIII. Phasing experimental SIR data with the replacing atoms in a centrosymmetric arrangement

A multisolution direct method has been proposed to resolve the phase ambiguity intrinsic in single isomorphous replacement data of proteins with the replacing atoms in a centrosymmetric arrangement, The phase ambiguity of each reflection is in fact a 'sign ambiguity' of the phase difference between the phase of the native protein and that of the replacing atoms, i.e. +/- \Delta phi\ = phi - phi. The P+ probability formula can be used to derive the signs. The multisolution phasing procedure is initiated using random starting values of P+. A cluster analysis is used instead of figures of merit to find the correct solution. The direct-method phases can be further improved by density-modification techniques. The method was tested with the experimental SIR data at 2 Angstrom resolution from a known protein aPP; satisfactory results were obtained.