Advances in X-ray crystallography have streamlined the process of determining high-resolution three-dimensional macromolecular structures. However, a rate-limiting step in this process continues to be the generation of crystals that are of sufficient size and quality for subsequent diffraction experiments. Here, iterative screen optimization (ISO), a highly automated process in which the precipitant concentrations of each condition in a crystallization screen are modified based on the results of a prior crystallization experiment, is described. After designing a novel high-throughput crystallization screen to take full advantage of this method, the value of ISO is demonstrated by using it to successfully crystallize a panel of six diverse proteins. The results suggest that ISO is an effective method to obtain macromolecular crystals, particularly for proteins that crystallize under a narrow range of precipitant concentrations.
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http://dx.doi.org/10.1107/S2053230X18017338 | DOI Listing |
Int J Mol Sci
December 2024
Bioinformatics and Molecular Design Research Center (BMDRC), Incheon 21983, Republic of Korea.
Understanding drug-target interactions is crucial for identifying novel lead compounds, enhancing efficacy, and reducing toxicity. Phenotype-based approaches, like analyzing drug-induced gene expression changes, have shown effectiveness in drug discovery and precision medicine. However, experimentally determining gene expression for all relevant chemicals is impractical, limiting large-scale gene expression-based screening.
View Article and Find Full Text PDFMaterials (Basel)
January 2025
School of Engineering, Computing and Mathematics, University of Plymouth, Plymouth PL4 8AA, UK.
The evaluation of the mechanical performance of fly ash-recycled mortar (FARM) is a necessary condition to ensure the efficient utilization of recycled fine aggregates. This article describes the design of nine mix proportions of FARMs with a low water/cement ratio and screens six mix proportions with reasonable flowability. The compressive strengths of FARMs were tested, and the influence of the water/cement ratio (/) and age on the compressive strength was analyzed.
View Article and Find Full Text PDFMicrob Cell Fact
January 2025
Chair of Technical Biochemistry, Technische Universität Dresden, Bergstraße 66, 01069, Dresden, Germany.
Background: The biosynthesis of the natural product family of the polycyclic tetramate macrolactams (PoTeMs) employs an uncommon iterative polyketide synthase/non-ribosomal peptide synthetase (iPKS/NRPS). This machinery produces a universal PoTeM biosynthetic precursor that contains a tetramic acid moiety connected to two unsaturated polyene side chains. The enormous structural and hence functional diversity of PoTeMs is enabled by pathway-specific tailoring enzymes, particularly cyclization-catalyzing oxidases that process the polyene chains to form distinct ring systems, and further modifying enzymes.
View Article and Find Full Text PDFLancet Gastroenterol Hepatol
January 2025
Department of Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
Background: Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.
Methods: This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America.
Purpose: Cancer-related financial toxicity occurs frequently and is a key driver of inequities in access to care and disparities in treatment outcomes. Current practices to screen for financial toxicity are inconsistent because of the lack of a validated and clinically integrated screening tool. This analysis aimed to create and assess an abbreviated version of the validated Comprehensive Score for Financial Toxicity (COST) tool, a measure of financial toxicity used for research purposes, which could easily be added into often-lengthy clinical screening workflows.
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