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SMARTSPIN® SCREENING

Accelerated by NMR​

SMARTSPIN® SCREENING

Accelerated by NMR

Ultra-fast NMR screening

Fragment-based drug discovery requires sensitive tools to detect even the weakest binding events. Traditional NMR has long been valued for this purpose but suffers from low sensitivity, high sample consumption, and long experiment times — often hours per sample.

SmartSpin® Technology, developed by NexMR and offered exclusively through CrystalsFirst, solves these challenges. It uses photo-hyperpolarization (photo-CIDNP), where pulses of light boost NMR signals dramatically. This innovation allows:

  • Detection of fragment binding in seconds to minutes instead of hours
  • Screening of hundreds to thousands of fragments per day
  • Reliable detection of weak, low-affinity binders at micromolar concentrations

In practical terms, SmartSpin® is 50–100 times faster and uses 30–50 times less protein and ligand material than conventional NMR.

Unique Throughput

Ultra-fast throughput — Up to ~700-1,500 samples screened per day, with automated flow setups enabling scalable screening.

Minimal sample requirements — Detect binding events at low micromolar protein and ligand concentrations, preserving scarce protein material.

Sensitive to weak interactions — Identifies weak or transient binders that often seed the most innovative chemistry.

Direct ligand-side detection — SmartSpin® measures interactions in solution without the need for labels or assay development.

Seamless integration — While its core value is standalone ultra-fast hit finding, SmartSpin® results can be immediately followed by crystallographic validation (SmartSoak®) and downstream design within the MAGNET platform.

Project Execution

  1. Sample preparation — Proteins and fragments prepared in SmartSpin®-compatible buffer.
  2. Light-induced hyperpolarization — Pulses of light polarize ligands, boosting their NMR signal.
  3. Binding detection — When a fragment binds the target, its polarized signal is quenched, enabling unambiguous detection.
  4. High-throughput screening — Automated workflows measure hundreds of samples in rapid succession.
  5. Hit triage and follow-up — Validated fragment hits can be prioritized for structural elucidation and fragment expansion.

Deliverables

  • NMR-validated fragment hit lists with quantitative binding readouts.
  • Binding profiles highlighting weak, medium, and strong interactions.
  • Integration-ready hits for crystallography and SmartSoak®
  • Comprehensive data package with spectra, polarization readouts, and QC.

FAQ: SMARTSPIN® SCREENING

SmartSpin®uses light-driven hyperpolarization (photo-CIDNP) to boost NMR signals. This reduces experiment time from hours to seconds, enabling true high-throughput fragment screening.

It detects binding down to low micromolar protein and ligand concentrations, including weak binders in the millimolar affinity range — interactions often missed by classical assays.

SmartSpin® can screen up to 1,000–1,500 samples per day with automation, compared to tens of samples per day with conventional NMR.

Hits can be seamlessly advanced into crystallographic validation (SmartSoak®) and structure-guided optimization within the MAGNET platform.

Because it reliably detects weak or unconventional binders, SmartSpin® provides critical starting points for designing molecular glues and PROTACs, where weak interactions are essential for ternary complex formation.

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