Does your model weigh the same as a Duck?
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Computer-aided drug design is a mature field by some measures, and it has produced notable successes that underpin the study of interactions between small molecules and living systems. However, unlike a truly mature field, fallacies of logic lie at the heart of the arguments in support of major lines of research on methodology and validation thereof. Two particularly pernicious ones are cum hoc ergo propter hoc (with this, therefore because of this) and confirmation bias (seeking evidence that is confirmatory of the hypothesis at hand). These fallacies will be discussed in the context of off-target predictive modeling, QSAR, molecular similarity computations, and docking. Examples will be shown that avoid these problems.
KeywordsCorrelation fallacy Confirmation bias QSAR Docking Off-targets Holy Grail
The authors gratefully acknowledge NIH for partial funding of the work (grant GM070481). Dr. Jain has a financial interest in BioPharmics LLC, a biotechnology company whose main focus is in the development of methods for computational modeling in drug discovery. Tripos Inc. has exclusive commercial distribution rights for Surflex-Dock and Surflex-Sim, licensed from BioPharmics LLC.
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