引领Discovery and Optimization

从碎片库质量检查，鸡尾酒设计和自动命中识别到结合（KD）的定量评估和配体的3D分析，从碎片库质量检查，鸡尾酒设计和自动命中识别到完整的工作流程。

Library Definition

• Quality check of fragment libraries with (Mnova齿轮,Verify&qNMR)
• 鸡尾酒设计MixDesign.

Library Screening

• Handling of screening sample withSampleJet
  
• Standard and customizable¹手¹⁹F NMR screening experiments can be run in automation
  
• High¹手¹⁹F sensitivity with CryoProbes (QCIF)
  
• Automated¹手¹⁹F hit detection with the integration of FBS with Mnova Screen

Structural Biology

Mnova Bindingautomatically processes protein-ligand titration 2D HSQC, tracks the peak movement and calculates the Kd’s for multiple peaks.

引领Optimization

The 3D conformations adopted by a free ligand in solution affects binding affinity for the pharmaceutical target. Their structural analysis helps to speed up lead optimization.
Mnova StereoFittergenerates 3D conformational populations using experimental NMR constraints (qNOE, chemical shift and J coupling).

• Automatic acquisition of¹手¹⁹F NMR experiments with IconNMR. Default experiments can be found in the Bruker library:
  -¹H NMR筛选实验具有缓冲/水抑制：¹H 1D, Saturation Transfer Difference,
  waterLOGSY,
  - T2 and T1rho
  -¹⁹F screening experiment with decoupling.
  
• TopSpin fragment-based-screening functionality bridges acquisition with analysis. Upon acquisition data are automatically analysed byMnova Screen. The results are reported in Mnova Screen in a Power-Point-like format.
  
• Protein-observed screening uses the Chemical Shifts Perturbation (CSP) method. H-C correlation experiment (HSQC) of the target with increasing amounts of ligand is then performed before the data is analyzed usingMnova Binding，这可以使数据和确定KD的确定。
  
• Mnova StereoFittercomputes the probability of 3D structural configurations and/or conformations, based on various forms of NMR experimental data input. Currently, StereoFitter can accept four distinct types of input to calculate the best 3D structure candidate(s): NOEs, RDCs, Js, and chemical shifts.
  
• 工作流可以充满Mnova DB, to store, for example, the screening data and 1D spectra of fragments which are frequently used during the fragment screening experiments.
  
  

• NMR sensitivity to fragment binding ideally matches the range of weak affinities where fragments are expected (Kd, the dissociation constant, is in the range of micromolar [μM] to several millimolar [mM])
• The NMR screening experiments offers both binding and ligands/s structural information
• NMR在实验确定溶液中的配体构象（3D分析）方面是独一无二的
• The selectivity and wide dispersion intrinsic to¹⁹F NMR,使¹⁹F screening an attractive method
  - It can accommodate up to 30 fragments in a mixture
  - High sensitivity owing to strong T2 effects
  - Selectivity: no fluor in protein samples
  -¹⁹F fragment libraries commercially available.
• Given that a typical screening can generate hundreds of spectra, automated and robust data analysis software enables lead discovery and optimization with minimal manual operations and superior reproducibility.
• 现在，所有所需的软件工具都包含在新的潜在客户发现和优化套件中。联系我们获取更多信息！