This grant is to advance methods of macromolecular crystallography and their implementation in the HKL/HKL2000 programs. This will be achieved by pursuing novel statistical methods and a novel approach to phasing. The integrated graphical command center will be expanded to include an expert system and automation. The implementation of this work will extend and improve the most widely used program system for data integration and scaling in the field. This grant is for: Advancing three-dimensional profile shape analysis, which will optimize the signal-to-noise ratio and allow for deconvolution of partially overlapping spots. It will also allow a proper model of the very sharp diffraction peaks obtained from pixel-array and diode-array detectors. Development of efficient phasing methods, which will be addressed by the use of non-isomorphism as a source of phase information. Highly redundant measurements will be used to analyze and separate the anomalous, radiation-induced and (potentially) other non-isomorphic components. A statistical phasing theory will be developed to optimally combine phases from modeling of non-isomorphisms with traditional sources of phases. Increasing the reliability of methods with an emphasis on high-throughput experiments, which will be addressed by an expert system that provides guidance for interactive data collection and analysis. The theory of information content for various stages of the crystallographic process will be developed and implemented. A formal measure of information content in collected or simulated data will be the basis for the decision-making process in the course of the experiment. To achieve these goals we will extend existing, integrated programs and also develop general, object oriented software modules for future crystallographic applications. The research and its implementation will increase the accuracy and reliability of 3-dimensional macromolecular structures, and will streamline the structure determination process.
| Zheng, Heping; Porebski, Przemyslaw J; Grabowski, Marek et al. (2017) Databases, Repositories, and Other Data Resources in Structural Biology. Methods Mol Biol 1607:643-665 |
| Dobosz-Bartoszek, Malgorzata; Pinkerton, Mark H; Otwinowski, Zbyszek et al. (2016) Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation. Nat Commun 7:12941 |
| Li, Wenlin; Schaeffer, R Dustin; Otwinowski, Zbyszek et al. (2016) Estimation of Uncertainties in the Global Distance Test (GDT_TS) for CASP Models. PLoS One 11:e0154786 |
| Alkire, R W; Rotella, F J; Duke, N E C et al. (2016) Taking a look at the calibration of a CCD detector with a fiber-optic taper. J Appl Crystallogr 49:415-425 |
| Porebski, Przemyslaw Jerzy; Cymborowski, Marcin; Pasenkiewicz-Gierula, Marta et al. (2016) Fitmunk: improving protein structures by accurate, automatic modeling of side-chain conformations. Acta Crystallogr D Struct Biol 72:266-80 |
| Minor, Wladek; Dauter, Zbigniew; Jaskolski, Mariusz (2016) The young person's guide to the PDB. Postepy Biochem 62:242-249 |
| Kikuchi, Sotaro; Borek, Dominika M; Otwinowski, Zbyszek et al. (2016) Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy. Proc Natl Acad Sci U S A 113:12444-12449 |
| Bromberg, Raquel; Grishin, Nick V; Otwinowski, Zbyszek (2016) Phylogeny Reconstruction with Alignment-Free Method That Corrects for Horizontal Gene Transfer. PLoS Comput Biol 12:e1004985 |
| Lee, Jyh-Yeuan; Kinch, Lisa N; Borek, Dominika M et al. (2016) Crystal structure of the human sterol transporter ABCG5/ABCG8. Nature 533:561-4 |
| Meyer, Peter A; Socias, Stephanie; Key, Jason et al. (2016) Data publication with the structural biology data grid supports live analysis. Nat Commun 7:10882 |
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