Predicting toxicity of benzene derivatives by molecular hologram derived quantitative structure-activity relationships (QSARS)

Holographic quantitative structure-activity relationship (HQSAR) is an emerging QSAR technique with the combined application of molecular hologram, which encodes the frequency of occurrence of various molecular fragment types, and the subsequent partial least squares (PLS) regression analysis. Based on molecular hologram, alignment-free QSAR models could be rapidly and easily developed with highly statistical significance and predictive ability. In this paper, the toxicity data for a series of 83 benzene derivatives to the autotrophic Chlorella vulgaris (IGC50, negative logarithmic form of 6-h 50% population growth inhibition concentration in mmol/l) were subjected to HQSAR analysis and this resulted in a model with a high predictive ability. The robustness and predictive ability of the model were validated by "leave-one-out" (LOO) cross-validation procedure and an external testing set. The influence of fragment distinction parameters and fragment size on the quality of the HQSAR model have been also discussed.