Mask‐based approach to phasing of single‐particle diffraction data. II. Likelihood‐based selection criteria

• Published in: Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2019-01, Vol.75 (1), p.79-89
• Main Authors: Lunin, Vladimir Y., Lunina, Natalia L., Petrova, Tatiana E., Baumstark, Manfred W., Urzhumtsev, Alexandre G.
• Format: Article
• Language: English
• Subjects: Chemical Sciences; Computer simulation; connectivity; Correlation coefficients; Cristallography; Criteria; Diffraction; Fourier Analysis; global searching; likelihood; Likelihood Functions; Masks; mask‐based approaches; Models, Molecular; Molecular structure; phase problem; Photosystem II; Photosystem II Protein Complex - chemistry; random masks; single‐particle data; Weight; X-Ray Diffraction - methods
• ISSN: 2059-7983; 0907-4449; 2059-7983; 1399-0047
• DOI: 10.1107/S2059798318016959

A new type of mask‐selection criterion is suggested for mask‐based phasing. In this phasing approach, a large number of connected molecular masks are randomly generated. Structure‐factor phases corresponding to a trial mask are accepted as an admissible solution of the phase problem if the mask satisfies some specified selection rules that are key to success. The admissible phase sets are aligned and averaged to give a preliminary solution of the phase problem. The new selection rule is based on the likelihood of the generated mask. It is defined as the probability of reproducing the observed structure‐factor magnitudes by placing atoms randomly into the mask. While the result of the direct comparison of mask structure‐factor magnitudes with observed ones using a correlation coefficient is highly dominated by a few very strong low‐resolution reflections, a new method gives higher weight to relatively weak high‐resolution reflections that allows them to be phased accurately. This mask‐based phasing procedure with likelihood‐based selection has been applied to simulated single‐particle diffraction data of the photosystem II monomer. The phase set obtained resulted in a 16 Å resolution Fourier synthesis (more than 4000 reflections) with 98% correlation with the exact phase set and 69% correlation for about 2000 reflections in the highest resolution shell (20–16 Å). This work also addresses another essential problem of phasing methods, namely adequate estimation of the resolution achieved. A model‐trapping analysis of the phase sets obtained by the mask‐based phasing procedure suggests that the widely used `50% shell correlation' criterion may be too optimistic in some cases. A new likelihood‐based estimate of the quality of randomly generated molecular masks has been suggested and tested in a mask‐based phasing procedure that was applied to simulated data for the photosystem II single particle. Using this selection criterion led to phase values that had 98% correlation with the true values for all 4000 reflections with resolution below 16 Å.