Alexander Metz

TL;DR: This work presents for the first time a computational strategy that simultaneously considers aspects of energetics and plasticity in the context of PPIM binding to a protein interface and introduces the PPIAnalyzer approach for identifying transient pockets on the basis of geometrical criteria only.

TL;DR: It is concluded that the frequently applied biophysical prescreening filters deteriorate the number of possible X-ray hits while only the immediate use of crystallography enables exhaustive retrieval of a maximum of fragment structures, which represent a rich source guiding hit-to-lead- to-drug evolution.

TL;DR: This review focuses on the general features of protein-protein interfaces, focusing on the characteristics that make them different from classical protein-ligand binding sites, as well as on problematic aspects that hamper the application of classical drug discovery approaches.

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: Thermodynamic profiles of ligand binding in solution indicate favorable entropic contributions to complex formation when large conformational adaptations in the dimer interface are involved, and suggests that stabilizing this non-productive subunit arrangement may be used as a further strategy for TGT inhibition.