Journal of Computer-Aided Molecular Design

, Volume 29, Issue 9, pp 847–865 | Cite as

Data quality in drug discovery: the role of analytical performance in ligand binding assays

  • Hermann WätzigEmail author
  • Imke Oltmann-Norden
  • Franziska Steinicke
  • Hassan A. Alhazmi
  • Markus Nachbar
  • Deia Abd El-Hady
  • Hassan M. Albishri
  • Knut Baumann
  • Thomas Exner
  • Frank M. Böckler
  • Sami El Deeb


Despite its importance and all the considerable efforts made, the progress in drug discovery is limited. One main reason for this is the partly questionable data quality. Models relating biological activity and structures and in silico predictions rely on precisely and accurately measured binding data. However, these data vary so strongly, such that only variations by orders of magnitude are considered as unreliable. This can certainly be improved considering the high analytical performance in pharmaceutical quality control. Thus the principles, properties and performances of biochemical and cell-based assays are revisited and evaluated. In the part of biochemical assays immunoassays, fluorescence assays, surface plasmon resonance, isothermal calorimetry, nuclear magnetic resonance and affinity capillary electrophoresis are discussed in details, in addition radiation-based ligand binding assays, mass spectrometry, atomic force microscopy and microscale thermophoresis are briefly evaluated. In addition, general sources of error, such as solvent, dilution, sample pretreatment and the quality of reagents and reference materials are discussed. Biochemical assays can be optimized to provide good accuracy and precision (e.g. percental relative standard deviation <10 %). Cell-based assays are often considered superior related to the biological significance, however, typically they cannot still be considered as really quantitative, in particular when results are compared over longer periods of time or between laboratories. A very careful choice of assays is therefore recommended. Strategies to further optimize assays are outlined, considering the evaluation and the decrease of the relevant error sources. Analytical performance and data quality are still advancing and will further advance the progress in drug development.


Drug discovery Biochemical assays Ligand binding assay Cell-based assays Precision Databases 



We gratefully acknowledge the financial support by the funding of King AbdulAziz University, Jeddah, Saudi Arabia, provided by Vice President Prof. Dr. A. O. AlYoubi. Furthermore, we are grateful to Dr. Christian Kramer for critically reading and improving our manuscript.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Hermann Wätzig
    • 1
    Email author
  • Imke Oltmann-Norden
    • 1
  • Franziska Steinicke
    • 1
  • Hassan A. Alhazmi
    • 1
  • Markus Nachbar
    • 1
  • Deia Abd El-Hady
    • 2
    • 3
  • Hassan M. Albishri
    • 4
  • Knut Baumann
    • 1
  • Thomas Exner
    • 5
  • Frank M. Böckler
    • 5
  • Sami El Deeb
    • 1
  1. 1.Institute of Medicinal and Pharmaceutical ChemistryTU BraunschweigBrunswickGermany
  2. 2.Chemistry Department, Faculty of ScienceUniversity of JeddahJeddahSaudi Arabia
  3. 3.Chemistry Department, Faculty of ScienceAssiut UniversityAssiutEgypt
  4. 4.Chemistry Department, Faculty of ScienceKing Abdulaziz UniversityJeddahSaudi Arabia
  5. 5.Pharmaceutical InstituteUniversity of TübingenTübingenGermany

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