A wealth of in silico tools is available for protein motif discovery and structural analysis. The aim of this chapter is to collect some of the most common and useful tools and to guide the biologist in their use. A detailed explanation is provided for the use of Distill, a suite of web servers for the prediction of protein structural features and the prediction of full-atom 3D models from a protein sequence. Besides this, we also provide pointers to many other tools available for motif discovery and secondary and tertiary structure prediction from a primary amino acid sequence. The prediction of protein intrinsic disorder and the prediction of functional sites and SLiMs are also briefly discussed. Given that user queries vary greatly in size, scope and character, the trade-offs in speed, accuracy and scale need to be considered when choosing which methods to adopt.
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http://dx.doi.org/10.1007/978-1-61779-176-5_21 | DOI Listing |
Acta Pharmacol Sin
January 2025
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
The bromodomain (BRD) represents a highly conserved structural module that provides BRD proteins with fundamental functionality in modulating protein-protein interactions involved in diverse biological processes such as chromatin-mediated gene transcription, DNA recombination, replication and repair. Consequently, dysregulation of BRD proteins has been implicated in the pathogenesis of numerous human diseases. In recent years, considerable scientific endeavors have focused on unraveling the molecular mechanisms underlying BRDs and developing inhibitors that target these domains.
View Article and Find Full Text PDFSci Rep
January 2025
Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule that has an immunosuppressive effect mediated by binding to immune inhibitory leukocyte immunoglobulin-like receptors (LILR) B1 and LILRB2. A conventional HLA-G isoform, HLA-G1, forms a heterotrimeric complex composed of a heavy chain (α1-α3 domains), β2-microglobulin (β2m) and a cognate peptide. One of the other isoforms, HLA-G2, lacks a α2 domain or β2m to form a nondisulfide-linked homodimer, and its ectodomain specifically binds to LILRB2 expressed in human monocytes, macrophages, and dendritic cells.
View Article and Find Full Text PDFFront Vet Sci
January 2025
Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
To fully characterize papillomavirus diversity in giant pandas (), we identified a novel papillomavirus (named AmPV5, GenBank accession number MZ357114) in oral swabs from giant pandas with the help of viral metagenomics technology in this study. The complete circular genome of AmPV5 is 7,935 bp in length, with a GC content of 39.1%.
View Article and Find Full Text PDFDespite extensive mapping of cis-regulatory elements (cREs) across cellular contexts with chromatin accessibility assays, the sequence syntax and genetic variants that regulate transcription factor (TF) binding and chromatin accessibility at context-specific cREs remain elusive. We introduce ChromBPNet, a deep learning DNA sequence model of base-resolution accessibility profiles that detects, learns and deconvolves assay-specific enzyme biases from regulatory sequence determinants of accessibility, enabling robust discovery of compact TF motif lexicons, cooperative motif syntax and precision footprints across assays and sequencing depths. Extensive benchmarks show that ChromBPNet, despite its lightweight design, is competitive with much larger contemporary models at predicting variant effects on chromatin accessibility, pioneer TF binding and reporter activity across assays, cell contexts and ancestry, while providing interpretation of disrupted regulatory syntax.
View Article and Find Full Text PDFJ Am Soc Mass Spectrom
January 2025
Analytical Characterization, Biologics Analytical Development, Technical Research & Development, Novartis Pharma AG, WKL693.3.20, Postfach, CH-4002 Basel, Switzerland.
Isomerization of aspartic acid residues is a relevant degradation pathway of protein biopharmaceuticals as it can impair their biological activity. However, the in silico prediction of isomerization hotspots and their consequences remains ambiguous and misleading. We have previously shown that all ion differential analysis (AiDA) of middle-down spectra can be used to reveal diagnostic terminal and internal fragments with more sensitivity than the conventional fragment ion mass matching methodology.
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