CHEM Pipeline for Small Molecules

General Description

The Core Facility for Crystallography and Biophysics offers services from small molecule crystallography, trough in vitro screening and biochemical and biophysical characterization to the structural biology of proteins and their complexes with ligands, including

  • Computational theoretical studies on small molecules and their complexes with cellular targets
  • Small molecule crystallization process
  • Small molecule properties and their polymorph analysis
  • Small molecules and protein X-ray crystallography
  • Protein engineering and expression
  • Biochemical and biophysical studies on ligand-target analysis.

Most services are optional (used as a stand-alone) and the sample may enter and exit CFCB pipeline (CHEM or BIO) at any point, or as a or all-in-one service. The appropriate reports are modular for that purpose.

Service Features

Phase Transitions (Solid state transformations)

Method or Service

  • TGA investigations
  • DSC studies
  • Thorough elucidation of the thermodynamic properties of the various forms

Report to Customer

  • TGA or DSC data
  • Interpretation of results

Polymorphism Analysis

Method or Service

Preliminary studies
  • Propensity screen including robotic high-throughput screening
Profile Study (detailed test of various conditions for crystallization process)
  • Solvent effects (polar, nonpolar)
  • Temperature
  • Kinetics vs. thermodynamic forms
  • Pseudopolymorphism (hydration, solvation)
  • Melting points
Amorphous Screens (analysis of different forms induced by various factors)
  • Solvent type, slow and fast evaporation
  • Slow and fast crystallization
  • Thermal and physical (e.g. grinding) effects

Report to Customer

  • Thermodynamic stability of forms and hydrates (solvates) with a reasonably high probability while keeping the experimental effort limited
  • First insight into complexity of the polymorphism for a given substance
  • Complete profiling of the polymorphic behavior
  • Amorphous screening report

Crystallization Trials

Method or Service

Initial screening and optimization
  • Crystallization via: batch, solvent evaporation, in-gel, concentration or diffusion gradient
  • Incubation at different temperatures
  • Different solvents and their mixtures
  • Additives
  • Homo- and heteroseeding
  • Solid state grinding approach
Visualization and crystallization drop scoring

Report to Customer

  • Temperature effect
  • Type of solvent
  • Composition of mixtures
  • Grinding conditions
  • Crystal shape (including photographs)
  • Characterization of all relevant polymorphs

Diffraction Data Collection

Method or Service

In-house diffraction data collection
Synchrotron trips and Neutron sources
  • Setting data collection strategy
  • Data collection and processing

Report to Customer

  • Copies of the data strategy and processing files
  • Crystals X-ray diffraction quality
  • All or preliminary diffraction images and statistics
  • Full diffraction dataset if collected successfully

Model Building

Method or Service

Structure solving and model building
  • Analysis of residuals
  • Applying methods beyond IAM (if feasible)

Report to Customer

  • Crystal Information File (CIF) and statistics
  • Files for full final refinement (ins and hkl files)
  • Model deposition (CSD and/or ICSD)

Sample and Data Storage
  • Samples, crystals or data can be handed over

Sample Preparation

The customer sample should be of sufficient quality, and its preparation is the responsibility of the customer.

Our recommendation and a prescreening procedure for acceptance of samples for crystallization trials in terms of sample quantity, concentration, amount (mg/mL), dispersity and buffer composition:

Single crystal experiment

Preferred crystal size 0.1 x 0.1 x 0.1 mm, with no cracks and well-defined faces, sample not reactive with air, not undergoing decomposition or phase transition during cooling to 100 K.

Powder experiment

Minimum amount 100 mg, pulverized with mortar, not reactive with air, not toxic

Our other chemical service modules (Phase Transitions or Polymorphism Analysis) may help in the preparation of the right small molecule, choosing the most favorable conditions. Most services are optional and the client sample may enter and exit our pipelines at any point, and the appropriate reports are modular for that purpose.

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