Core Concept The central idea is "Target-based Drug Discovery." Instead of screening compounds on whole cells or organisms (phenotypic screening), you start with a specific protein (e.g., a kinase, receptor, ion channel) implicated in a disease. Services then help you understand that target and find molecules that modulate it. Categories of Protein Target Services These services typically follow the drug discovery pipeline: 1. Target Identification & Validation Bioinformatics & Omics Analysis: Mining genomic, proteomic, and clinical data to identify novel disease-associated targets. Genetic Validation: CRISPR/Cas9 gene editing (knock-out/knock-in), siRNA/shRNA knockdown to confirm the target's role in disease pathways. Functional Validation: Cell-based assays to see if modulating the target affects disease-relevant phenotypes. 2. Protein Expression & Purification Recombinant Protein Production: Cloning, expressing (in E. coli, insect, or mammalian cells), and purifying milligram to gram quantities of the target protein. This is essential for structural studies and biochemical assays. Membrane Protein Expertise: Specialized services for difficult-to-express targets like GPCRs and ion channels. Tagging & Labeling: Adding tags (His, GST, FLAG) for purification or fluorescent/isotopic labels for assays. 3. Structural Biology & Biophysics X-ray Crystallography: Determining high-resolution 3D structures of protein-ligand complexes. Cryo-Electron Microscopy (Cryo-EM): For large complexes or membrane proteins unsuitable for crystallography. Nuclear Magnetic Resonance (NMR) Spectroscopy: For studying dynamics and ligand binding in solution. Surface…
Traditional SELEX (Systematic Evolution of Ligands by EXponential enrichment) is a method to select high-affinity, specific nucleic acid aptamers from a vast random library (10¹³-10¹⁵ sequences). The bottleneck has always been the final cloning and Sanger sequencing of only a few dozen candidates, which often misses rare, high-performance aptamers. NGS-assisted SELEX integrates Next-Generation Sequencing at multiple rounds of the SELEX process. This provides a massive, data-rich view of the entire evolutionary landscape, enabling intelligent selection and identification of the best aptamers. Typical Workflow of an NGS-Assisted SELEX Service A professional service provider will manage this entire pipeline: Project Design & Library Synthesis: Collaboration to define target (protein, small molecule, cell), counter-selection requirements, and library design (random region length, fixed primers for NGS). Parallel SELEX Execution: Performing the iterative selection process (binding, partitioning, amplification) across multiple rounds (usually 8-12). Key NGS Integration Points: Initial Library Analysis: Sequencing the naive library to confirm diversity and complexity. Monitoring Rounds (e.g., Rounds 3, 6, 9): Taking small samples from intermediate rounds for NGS. This is the critical advantage. It tracks: Sequence Enrichment: Which families are becoming more abundant. Diversity Collapse: When to stop selection before losing good candidates. Informed Decision-Making: Data guides adjustments in selection stringency for subsequent rounds. Final Round Deep Sequencing: Comprehensive NGS of…
