A structure guided QSAR: A rapid and accurate technique to predict IC50: A case study

Rama K Mishra*, Jasbir Singh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


In this study, the role of highly structured water molecules present in the active site of the leukotriene A4 hydrolase (LTA4H) enzyme has been critically examined through the docking experiments. It was observed that different experiments were necessary to perform the docking studies. The ligands capable of displacing or interacting with bound-water(s) displayed different binding poses as well as the scores. The docking scores E (CvdW) from Glide and ChemScore (CS) from FlexX, with and without bound-waters, obtained through different docking experiments were used to construct two structure guided bi-parametric linear regression models using the IC50enzyme activity data. The predictive squared correlation coefficients (Q2) obtained for these models, with and without bound waters, were found to be 0.73 and 0.67, respectively. These models were validated using test and validated sets of compounds. Utilizing these QSAR models, 409 proposed structures were docked and their respective predicted IC50data were generated. From the in-silico evaluation of these 409 proposed structures representing diverse chemotypes, 39 compounds were triaged, synthesized and evaluated in the enzyme inhibition assay. The predicted and experimental biological data (IC50) was correlated and the square of the correlation coefficient (R2) between the observed and calculated IC50was found to be 0.87

Original languageEnglish (US)
Pages (from-to)152-163
Number of pages12
JournalCurrent Computer-Aided Drug Design
Issue number2
StatePublished - Sep 1 2015


  • Crystallographic waters
  • Docking
  • Scoring function
  • Structure based QSAR

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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