Computational Approaches and Methodologies in Proximity Induced Pharmacology

Explore computational approaches and methodologies in proximity-induced pharmacology in this 22-minute conference talk presented by Evianne Rovers from SGC, University of Toronto at MolSoft's UGM 2023. Delve into the world of PROTACs and their advantages over traditional small molecule drugs, focusing on their ability to induce protein degradation through ubiquitination. Examine structural analysis techniques for identifying non-catalytic pockets in enzyme structures and discover how this approach can lead to novel pockets with chemical matter ready for incorporation into ProxPharm compounds. Investigate the potential of computational tools in predicting crystal structures of ternary complexes and evaluate their efficiency in virtual screening for PROTAC activity. Consider two possible strategies for optimizing PROTAC screening and explore the hypothesis that distance could be a critical factor in PROTAC activity.

Intro
PROTACS induce degradation of target proteins by ubiquitination
PROTACS have advantages over traditional small molecule drugs
Structural analysis to identify non-catalytic pockets in enzyme structures
Approach identified novel pockets with chemical matter ready to be incorporated into ProxPharm compounds
Can computational tools predict crystal structures of ternary complexes accurately?
Efficiency in predicting PROTAC activity in virtual screening is unclear
Two possible strategies to optimize PROTAC screening
We hypothesized that distance could be critical for PROTAC activity