ABSTRACT
The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.psi.ch) is introduced: a platform crafted using state-of-the-art software architecture and web technologies for sample management of rotational data experiments. The HEIDI webpage features a data-review tab for enhanced result visualization and provides programmatic access through a representational state transfer application programming interface (REST API). The migration of the local FFCS MongoDB instance to the cloud is highlighted and detailed. This transition ensures secure, encrypted and consistently accessible data through a robust and reliable REST API tailored for the FFCS software suite. Collectively, these advancements not only significantly elevate the user experience, but also pave the way for future expansions and improvements in the capabilities of the system.
Subject(s)
Drug Discovery , High-Throughput Screening Assays , Software , High-Throughput Screening Assays/methods , Drug Discovery/methods , User-Computer Interface , Small Molecule Libraries , Crystallography, X-Ray/methodsABSTRACT
PSD-95/SAP90 is a member of the MAGUK superfamily. In excitatory synapses, PSD-95 clusters receptors and ion channels at specific sites in the postsynaptic membrane and organizes downstream signaling and cytoskeletal molecules. We have determined the crystal structures of the apo and GMP-bound forms to 2.3 and 2.0 A resolutions, respectively, of a fragment containing the SH3, HOOK, and guanylate kinase (GK) domains of PSD-95. We observe an intramolecular interaction between the SH3 and GK domains involving the formation of a beta sheet including residues N- and C-terminal to the GK domain. Based on amino acid conservation and mutational data available in the literature, we propose that this intramolecular interaction is a common feature among MAGUK proteins.
Subject(s)
Catalytic Domain , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/metabolism , Nucleoside-Phosphate Kinase/chemistry , Nucleoside-Phosphate Kinase/metabolism , src Homology Domains , Amino Acid Sequence , Animals , Apoenzymes/chemistry , Apoenzymes/metabolism , Binding Sites , Crystallography, X-Ray , Disks Large Homolog 4 Protein , Guanosine Monophosphate/metabolism , Guanylate Kinases , Intracellular Signaling Peptides and Proteins , Membrane Proteins , Models, Molecular , Molecular Sequence Data , Protein Binding , Protein Structure, Quaternary , Protein Structure, Secondary , Protein Structure, Tertiary , Rats , Sequence Alignment , Static Electricity , Structure-Activity RelationshipABSTRACT
The symmetry elements detected by the self-rotation and the Patterson functions, associated to strong correlations between the positions of the molecules in the asymmetric unit, are used to reduce the effective number of independent bodies to be located by the molecular replacement method. A distinction is made between 'frustrated' crystallographic symmetries, i.e. those that are almost crystallographic ones, and 'standard' non-crystallographic symmetries, which are taken into account by specific techniques. These have been successfully applied to many-body macromolecular crystal structures, with important savings in time and computational effort.
