phenix.refine is a program within the PHENIX package that supports crystallographic structure refinement against experimental data with a wide range of upper resolution limits using a large repertoire of model parameterizations. It has several automation features and is also highly flexible. Several hundred parameters enable extensive customizations for complex use cases. Multiple user-defined refinement strategies can be applied to specific parts of the model in a single refinement run. An intuitive graphical user interface is available to guide novice users and to assist advanced users in managing refinement projects. X-ray or neutron diffraction data can be used separately or jointly in refinement. phenix.refine is tightly integrated into the PHENIX suite, where it serves as a critical component in automated model building, final structure refinement, structure validation and deposition to the wwPDB. This paper presents an overview of the major phenix.refine features, with extensive literature references for readers interested in more detailed discussions of the methods.
A structure determination in combination with a kinetic study of the steroid converting isozyme of horse liver alcohol dehydrogenase, SS-ADH, is presented. Kinetic parameters for the substrates, 5beta-androstane-3beta,17beta-ol, 5beta-androstane-17beta-ol-3-one, ethanol, and various secondary alcohols and the corresponding ketones are compared for the SS- and EE-isozymes which differ by nine amino acid substitutions and one deletion. Differences in substrate specificity and stereoselectivity are explained on the basis of individual kinetic rate constants for the underlying ordered bi-bi mechanism. SS-ADH was crystallized in complex with 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan -24-acid (cholic acid) and NAD(+), but microspectrophotometric analysis of single crystals proved it to be a mixed complex containing 60-70% NAD(+) and 30-40% NADH. The crystals belong to the space group P2(1) with cell dimensions a = 55.0 A, b = 73.2 A, c = 92.5 A, and beta = 102.5 degrees. A 98% complete data set to 1.54-A resolution was collected at 100 K using synchrotron radiation. The structure was solved by the molecular replacement method utilizing EE-ADH as the search model. The major structural difference between the isozymes is a widening of the substrate channel. The largest shifts in C(alpha) carbon positions (about 5 A) are observed in the loop region, in which a deletion of Asp115 is found in the SS isozyme. SS-ADH easily accommodates cholic acid, whereas steroid substrates of similar bulkiness would not fit into the EE-ADH substrate site. In the ternary complex with NAD(+)/NADH, we find that the carboxyl group of cholic acid ligates to the active site zinc ion, which probably contributes to the strong binding in the ternary NAD(+) complex.
Author(s): Poon, Billy K.; Zwart, Peter H.; Adams, Paul D.; Sauter, Nicholas K. | Abstract: With the advances in structure refinement software that can automatically solve structures and the increasing use of robotics at synchrotron beamlines, high throughput crystallography is becoming much more automated. However, one aspect of the process that still requires a certain level of human intervention is during data collection. Web-Ice (Gonzalez A, Moorhead P, McPhillips SE, Song J, Sharp K, Taylor JR, Adams PD, Sauter NK, and Soltis SM, (2008) J. Appl. Cryst. 41(1), in press), jointly developed at the Stanford Synchrotron Radiation Laboratory and the Lawrence Berkeley National Laboratory, aims to address this issue by providing beamline users with a unified, graphical user interface that couples the low level control of the beamline hardware with the processing software (LABELIT, DISTL, MOSFLM) responsible for converting raw diffraction images into data sets suitable for refinement. Web-Ice can also perform automated crystal screening for selecting the best samples and calculation of the optimal strategy for data collection. Recent developments in Web-Ice include automatic handling of ice rings at varying two theta angles, automatic selection of the appropriate space group, and automatic data integration and scaling. Through Web-Ice, the beamline user can be more efficient at the synchrotron by allowing the software to handle the decision making for data collection in routine cases, while retaining the flexibility for more difficult data sets by providing a more user friendly interface for tweaking various parameters and customization of scripts for the data processing software.
algorithms have propelled advances in artificial intelligence and represent a foundational research area in advancing AI for Science. Future advancements in DOE Office of Science priority areas such as climate science, astrophysics, fusion, advanced materials, combustion, and quantum computing all require randomized algorithms for surmounting challenges of complexity, robustness, and scalability. This report summarizes the outcomes of that workshop, Randomized Algorithms for Scientific Computing (RASC), held virtually across four days in December 2020 and January 2021.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
