Postmodern Transgressions in Structural Biology: The Road to Scientific Serfdom.
Bernhard Rupp
Division of Forensic Crystallography
k.k. Hofkristallamt
Vista, CA 92084
Department of Genetic Epidemiology
Innsbruck Medical University
Innsbruck (Austria)
Fundamental scientific epistemology requires that a strong claim is supported by strong and convincing proof. As an example, the proposition of a ligand bound to a target protein in a precise conformation and pose presents a very strong claim, and confirming (positive omit difference) electron density will provide the correspondingly strong experimental evidence. A survey of ligand structure models has revealed that in an unexpectedly large number of ligand structures, the required electron density is not present or does not sufficiently support the proposed ligand pose. Of great concern is that many of these fictitious models are used in support of bio-medically relevant hypotheses, which in turn raises the question to what degree the progress of science is delayed by unsupported claims: grants cannot be funded when they contradict models believed to be true, and millions of taxpayer money can be squandered by trying to pursue subsequent science based on false premises. The apparent lack of consequences for poor and at minimum self-deceptive work threatens to become systemic and accepted over the course of time, unless young scientists themselves resist the postmodern relativism leading to erosion of credibility of their profession and take full responsibility for their exciting and important work.