SHARP :MAXIMUM-LIKELIHOOD REFINEMENT OF HEAVY-ATOM PARAMETERS IN THE MIR AND MAD METHODS. Éric. de La Fortelle and Gérard. Bricogne, MRC-LMB, Hills Road, Cambridge CB2 2QH, England.

The problem of estimating heavy-atom parameters (esp. occupancies) from acentric reflexions in the MIR method has a long history of difficulties, and a conceptually satisfactory solution allowing bias-free refinement of all parameters (including the lack of isomorphism) has only recently been obtained by a recourse to the method of maximum-likelihood estimation [1,2]. The situation is essentially identical in the case of MAD phasing. The maximum-likelihood method needs to be invoked to exploit incomplete phase information in a heavy-atom parameter refinement while preventing that information from biasing the results.

We have designed and written from scratch a computer program -_SHARP_(Statistical Heavy-Atom Refinement and Phasing) - that fully implements the maximum-likelihood approach. It can refine simultaneously the scale factors, a parametrised model for the lack of isomorphism and all heavy-atom parameters from MIR and MAD data, or any mixture of them. The program performs in conformity with theoretical requirements on simulates data, and all tests on measured datasets have shown satisfactory results, outperforming the classical program MLPHARE[2]. The likelihood function has also been used as a detection tool, especially to plot residual Fourier maps and probe for minor sites.

Special care has been taken to make the program user-friendly. A self-explanatory graphical user interface has been set up, based on hypertext tools, so that SHARP can be run from anywhere through an Internet connection. The use of the software and interface will be demonstrated.

The next developments will include automatic heavy-atom detection, validation of further model hypotheses (new sites etc.) on a fraction of the data unused in the refinement, and a two-way connection to program BUSTER for further phase improvement, e.g. by mode permutation.

References

[1] Bricogne, G. (1991). In Isomorphous Replacement and Anomalous Scattering, edited by W. WOLF, P.R. Evans & A.G.W Leslie, pp. 60-68. Warrington : SERC Daresbury Laboratory.

[2] Otwinowski, Z. (1991). In Isomorphous Replacement and Anomalous Scattering, edited by W. WOLF, P.R. Evans & A.G.W Leslie, pp. 60-68. Warrington : SERC Daresbury Laboratory.

[3] Bricogne, G. (1993). Acta Cryst. D49, 37-60.