Towards a black-box for biological EXAFS data analysis. II. Automatic BioXAS Refinement and Analysis (ABRA).

In biological systems, X-ray absorption spectroscopy (XAS) can determine structural details of metal binding sites with high resolution. Here a method enabling an automated analysis of the corresponding EXAFS data is presented, utilizing in addition to least-squares refinement the prior knowledge about structural details and important fit parameters. A metal binding motif is characterized by the type of donor atoms and their bond lengths. These fit results are compared by bond valance sum analysis and target distances with established structures of metal binding sites. Other parameters such as the Debye-Waller factor and shift of the Fermi energy provide further insights into the quality of a fit. The introduction of mathematical criteria, their combination and calibration allows an automated analysis of XAS data as demonstrated for a number of examples. This presents a starting point for future applications to all kinds of systems studied by XAS and allows the algorithm to be transferred to data analysis in other fields.

On the combination of molecular replacement and single-wavelength anomalous diffraction phasing for automated structure determination.

A combination of molecular replacement and single-wavelength anomalous diffraction phasing has been incorporated into the automated structure-determination platform Auto-Rickshaw. The complete MRSAD procedure includes molecular replacement, model refinement, experimental phasing, phase improvement and automated model building. The improvement over the standard SAD or MR approaches is illustrated by ten test cases taken from the JCSG diffraction data-set database. Poor MR or SAD phases with phase errors larger than 70 degrees can be improved using the described procedure and a large fraction of the model can be determined in a purely automatic manner from X-ray data extending to better than 2.6 A resolution.

Auto-rickshaw: an automated crystal structure determination platform as an efficient tool for the validation of an X-ray diffraction experiment.

The EMBL-Hamburg Automated Crystal Structure Determination Platform is a system that combines a number of existing macromolecular crystallographic computer programs and several decision-makers into a software pipeline for automated and efficient crystal structure determination. The pipeline can be invoked as soon as X-ray data from derivatized protein crystals have been collected and processed. It is controlled by a web-based graphical user interface for data and parameter input, and for monitoring the progress of structure determination. A large number of possible structure-solution paths are encoded in the system and the optimal path is selected by the decision-makers as the structure solution evolves. The processes have been optimized for speed so that the pipeline can be used effectively for validating the X-ray experiment at a synchrotron beamline.

Towards complete validated models in the next generation of ARP/wARP.

The design of a new versatile control system that will underlie future releases of the automated model-building package ARP/wARP is presented. A sophisticated expert system is under development that will transform ARP/wARP from a very useful model-building aid to a truly automated package capable of delivering complete, well refined and validated models comparable in quality to the result of intensive manual checking, rebuilding, hypothesis testing, refinement and validation cycles of an experienced crystallographer. In addition to the presentation of this control system, recent advances, ideas and future plans for improving the current model-building algorithms, especially for completing partially built models, are presented. Furthermore, a concept for integrating validation routines into the iterative model-building process is also presented.