Structural Biology

Our Customized Structural Biology Platform

WuXi Biology and Testing’s structural biology platform delivers customized and integrated solutions in drug discovery, X-ray crystallography, CryoEM, NMR, premium protein supply, biophysical analysis, and fragment screening.

Capabilities at a Glance

High-quality protein production
>10 orthogonal biophysical assays and screening systems
>200 targets ready for XPRESS complex structure solution with client ligands
Fragment-based screening with >3,000-member novel fragment library
Cryo-EM
Cell-based thermal shift assays for target engagement

Comprehensive Protein Production and Target Expertise

We produce high-quality recombinant proteins tailored to meet every drug developer's scientific needs. Through our PRIME PROTEIN program, we continuously drive innovation in expression systems and purification processes to generate stringently quality-controlled proteins for use in functional assays, high-throughput screening, cryo-EM, and crystallization. Recombinant proteins can be expressed in E. coli, insect, and mammalian systems in milligram to gram quantities.

For hit validation and characterization, target proteins are produced using our highly parallelized expression and purification workflows. Decades of scientific expertise enable our teams to successfully generate challenging targets and macromolecular complexes, including:

Membrane proteins (ion channels, transporters, GPCRs, etc.)
Secreted proteins and cell-surface receptors
Metabolic enzymes, proteases, and phosphatases
Kinases, epigenetic regulators, and nuclear receptors

Utilizing our proprietary bi-turbo vector system, target proteins are expressed in parallel across bacterial and insect systems from identical plasmid constructs. These vectors feature specialized promoters for optimal recombinant protein expression timing, while optimized viral DNA backbones enable co-expression of critical factors to enhance overall yield and structural homogeneity. Furthermore, we offer customized mammalian cell expression (such as HEK systems) and stable isotope labeling for specialized biophysical studies. Every recombinant protein undergoes rigorous quality control and stability testing to ensure strict compliance with program specifications.

Assay Grade Protein Production

Protein Complexes 1 — Protein Complexes: AMPK – AMP activated protein

Dna Modifying Proteins 2 — DNA Modifying Proteins: SMARCA2 – transcriptional regular / chromatin remodeling

Immune Therapy And Rare Diseases 1 — Immune Therapy: cGAS-DNA sensor in the STING pathway

Immune Therapy Rare Disease 1 — Rare Diseases: STING-stimulator of interferon genes

Seamless Platform from Protein Production to Structure-Based Drug Design

Cancer and Inflammation: ATM, AMPK, NEK7, PI3K, ROR1, SRC, ULK1, WEE1, NLRP3, KRAS
Membrane Proteins: Glucose transporter, P2X3, GPR40, CNR1, β2AR
DNA Damage Response: ATM, ATR/ATRIP, CHK1, CHK2, CDKs, cyclins
Neurodegeneration: BACE1, PDE, NFE2L2, PTPN1, MAO-B, NTRK1, JNKs
RNA/DNA Mod. Proteins: Cas9, FEN1, EME1, RIG-I, SND1, WRN, SMARCAs
Epigenetic Targets: BRD2, BAZ1A, CREBBP, SIRTuins, HDACs, EHMT1
Immune System: cGAS, STING, IL1, ILRL1, MMPs, antibodies

Biopharmaceutical Assays Protein Stability and Aggregation

We provide highly accurate characterization of protein stability by analyzing thermal unfolding, aggregation, and chemical denaturation using nanoDSF technology — an advanced Differential Scanning Fluorometry method.

Advantages of nanoDSF Technology:

Native – label- and dye-free conditions, any buffer
Precise – ultra-high resolution
Fast – 48 capillaries within 3 seconds
Broad – all target classes, concentrations from 5 µg/ml to > 250 mg/ml
Efficient – low sample consumption

Application Areas for Biologics and Membrane Proteins:

Buffer and formulation screening and optimization
Quality control
Stability screening for antibodies in cell culture supernatants

The development of biologics requires precise biophysical analytics across all stages in the process. Utilizing nanoDSF technology, we measure protein melting curves under label-free conditions by tracking intrinsic tryptophan fluorescence, enabling accurate assessments in virtually any buffer system or additive mixture, including detergents.

Moreover, the dynamic range of simultaneously measurable concentrations spans from 150 mg/ml down to 5 μg/ml in a working volume of 10 μl. The technology is used to analyze protein quality and stability, with applications including protein engineering, formulation development and batch-to-batch comparison.

For our clients, we can analyze:

Tm – Thermal unfolding
Tagg – Temperature onset of aggregation
Cm – Chemical unfolding
DeltaG – Free folding energy and prediction of long-term stability

We’re currently operating the Prometheus NT.48 from NanoTemper with its advantageous low sample consumption and a broad concentration range from ng/mL to mg/ml.

Fragment-Based Drug Discovery

We provide fast and cost-efficient hit identification through targeted fragment screening and virtual high-throughput screening strategies. To support your discovery programs, we maintain curated fragment libraries comprising thousands of diverse, low-molecular-weight compounds.

Custom proprietary libraries can also be seamlessly integrated into our high-throughput screening workflows. Following primary screening, validated hit candidates undergo orthogonal biophysical confirmation and structural characterization using:

Surface Plasmon Resonance (SPR)
MicroScale Thermophoresis (MST)
Differential Scanning Fluorometry (DSF / nanoDSF)
Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS)

Validated hits can be subjected to crystallization to obtain structural information.

Related Graphs

Screening Fbdd 1 — Screening | Microscale thermophoresis (MST) and temperature related intensity change (TRIC)

Hit Confirmation Spr Fbdd — Hit Confirmation | Surface Plasmon Resonance (SPR)

Hit Confirmation Fbdd — Hit Confirmation | Nanoscale differential scanning fluorimetry (nanoDSF)

Biophysical Assays and Screening

We have established a comprehensive suite of biophysical and biochemical assay methodologies that can be customized to meet the specific requirements of your drug development program. Our INTRACT platform comprises various biophysical assays methods and low- to medium-throughput screening. It is ideally suited for fragment screening or validation of compounds from focused libraries, HTS hits or collections generated from virtual screening approaches.Our biophysical assay platform includes measurements of enzymatic activities, on/off binding kinetics, KD analyses and protein stability determination. The INTRACT biophysical analytics and screening platform is made of a versatile series of orthogonal assay technologies for hit validation including:

DSF / nanoDSF
Alpha Screen
Enzyme Activity
Fluorescence Cross-Correlation Spectroscopy*
Fluorescence Polarization Assays
Kinetic Assays
LC-MS Screening*
Microscale Thermophoresis (MST)
NMR Screening*
SPR
SwitchSENSE

Our robotics-enhanced screening platform provides efficient, cutting-edge technologies for protein biophysical services and for the analysis and validation of compounds. Thus, INTRACT enables highly accurate and sensitive measurements under close-to-native conditions to reliably guide the optimization of your compounds.

The platform can also be used for fast and reliable control of protein quality, measuring bimolecular interactions such as protein-protein, fragment-protein binding, and the analysis of DNA, RNA, peptide or antibody interactions. Additionally, INTRACT can be added to any computational chemistry or crystallography project to analyze fragment interactions with the respective target proteins in more detail, making INTRACT perfectly suited to cross-validate and prioritize compounds for co-crystallization.

X-Ray Crystallography

We offer end-to-end structural generation solutions for challenging drug targets, delivering high-resolution atomic data to guide rational lead optimization and candidate selection.

Through our standardized XPRESS portfolio of disease-relevant targets, our rapid-turnaround XPEDITE program for published constructs, and our fully customized XPERT solutions for de novo structures, we provide tailored crystal structure determination for complex macromolecular targets.

Learn More

CryoEM Structural Determination

Cryo-electron microscopy (CryoEM) enables high-resolution structural determination of large macromolecular assemblies, membrane proteins, and complex biological targets without the need for crystallization.

We provide tailored protein expression, sample optimization, negative staining, and single-particle Cryo-EM workflows to resolve challenging structures under near-native conditions.

Learn More

Microscale Thermophoresis

WuXi Biology and Testing is an experienced global provider of MicroScale Thermophoresis (MST) technologies. MST services include assay development, protein supply for MST (or other assays), fragment screening, fragment or hit validation, and various interaction studies.

For eight years, we have successfully applied MST with Monolith NT, 115 NT, LabelFree, and NT automated devices for hit and fragment validation, making us an experienced laboratory testing partner for MST.