Maren Kuhnert

TL;DR: While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.

TL;DR: An empirical metrics that might serve as an indicator during lead optimization to qualify compounds as candidates for structural revalidation are suggested, in which minor chemical modifications within one inhibitor series lead to surprisingly different binding modes.

TL;DR: The most potent inhibitor of this series exhibits two-digit nanomolar affinity and represents, to the best of the authors' knowledge, the most potent nonpeptidic inhibitor of HTLV-1 PR described so far.

TL;DR: The first crystal structure in complex with a nonpeptidic inhibitor that accounts for rationalizing the rather moderate affinity of Indinavir against HTLV-1 PR is described and provides the basis for further structure-guided optimization strategies.

TL;DR: There are a number of interesting case studies, some of which are discussed in detail, which highlight that the hypothesis that similar ligands bind in a similar fashion does not hold true on a comprehensive basis.