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

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Abstract

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.

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Notes

  1. ACE can also deal with impure samples.

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Acknowledgments

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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    Authors and Affiliations

    1. Institute of Medicinal and Pharmaceutical Chemistry, TU Braunschweig, Beethovenstr. 55, 38106, Brunswick, Germany

      Hermann Wätzig, Imke Oltmann-Norden, Franziska Steinicke, Hassan A. Alhazmi, Markus Nachbar, Knut Baumann & Sami El Deeb

    2. Chemistry Department, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia

      Deia Abd El-Hady

    3. Chemistry Department, Faculty of Science, Assiut University, Assiut, 71516, Egypt

      Deia Abd El-Hady

    4. Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, 80203, Saudi Arabia

      Hassan M. Albishri

    5. Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany

      Thomas Exner & Frank M. Böckler

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    1. Hermann Wätzig
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    Correspondence to Hermann Wätzig.

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    Hermann Wätzig and Imke Oltmann-Norden have equally contributed to this paper.

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    Wätzig, H., Oltmann-Norden, I., Steinicke, F. et al. Data quality in drug discovery: the role of analytical performance in ligand binding assays. J Comput Aided Mol Des 29, 847–865 (2015). https://doi.org/10.1007/s10822-015-9851-6

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    • DOI: https://doi.org/10.1007/s10822-015-9851-6

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