Classifying Calpain Inhibitors for the Treatment of Cataracts: A Self Organising Map (SOM) ANN/KM Approach in Drug Discovery

  • I. L. HudsonEmail author
  • S. Y. Leemaqz
  • A. T. Neffe
  • A. D. Abell
Part of the Studies in Computational Intelligence book series (SCI, volume 628)


Calpain inhibitors are possible therapeutic agents in the treatment of cataracts. These covalent inhibitors contain an electrophilic anchor (“warhead”), an aldehyde that reacts with the active site cysteine. Whilst high throughput docking of such ligands into high resolution protein structures (e.g. calpain) is a standard computational approach in drug discovery, there is no docking program that consistently achieves low rates of both false positives (FPs) and negatives (FNs) for ligands that react covalently (via irreversible interactions) with the target protein. Schroedinger’s GLIDE score, widely used to screen ligand libraries, is known to give high false classification, however a two-level Self Organizing Map (SOM) artificial neural network (ANN) algorithm, with KM clustering proved that the addition of two structural components of the calpain molecule, number hydrogen bonds and warhead distance, combined with GLIDE score (or its partial energy subcomponents) provide a superior predictor set for classification of true molecular binding strength (IC50). SOM ANN/KM significantly reduced the number of FNs by 64 % and FPs by 26 %, compared to the glide score alone. FPs were shown to be mostly esters and amides plus alcohols and non-classical, and FNs mainly aldehydes and ketones, masked aldehydes and ketones and Michael.


Virtual Screening Good Binder Calpain Inhibitor Best Match Unit Michael Acceptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • I. L. Hudson
    • 1
    Email author
  • S. Y. Leemaqz
    • 2
  • A. T. Neffe
    • 3
  • A. D. Abell
    • 4
  1. 1.School of Mathematical and Physical SciencesThe University of NewcastleNSWAustralia
  2. 2.Robinson Research InstituteThe University of AdelaideAdelaideAustralia
  3. 3.Institute of Biomaterial ScienceHelmholtz-Zentrum GeesthachtTeltowGermany
  4. 4.School of Physics and ChemistryThe University of AdelaideAdelaideAustralia

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