TDSIR PHASING - DIRECT USE OF PHASE-INVARIANT DISTRIBUTIONS IN MACROMOLECULAR CRYSTALLOGRAPHY

A new strategy for employing three phase triples invariant estimates f rom Hauptman's single isomorphous replacement (SIR) and anomalous disp ersion (SAS) joint probability distribution formulae is outlined which produces a single unique phase-invariant solution in the case where t he positions of the heavy-atom scatterers is known. A similar but non- identical result is obtained for the phase invariants of a structure f or which a molecular-replacement solution has been obtained. It is imp ortant to note that the values of the individual native/derivative pha ses can be determined directly from the probability distribution formu lae without having to utilize the phase invariant estimates in an acti ve way. Elimination of the multisolution aspect of utilizing phase-inv ariant estimates should have important repercussions with regard to ph asing macromolecular sets of derivatized data. Trial calculations base d on experimentally measured 2.5 Angstrom data for three derivatives o f cytochrome c(550) are encouraging. The average of the three SIR maps resolves a number of structural ambiguities seen in the published mul tiple isomorphous replacement (MIR) map obtained from eight derivative s.