Computational Peptide Design Pipelines for Informing Wet-Lab Experiments

Chemists continue to increase the number of building blocks from which peptide macrocycles may be synthesized; however, this creates an astronomical number of possible peptide sequences that one could synthesize.  How are we to choose the sequences that we will synthesize, particularly for drug discovery?  In the last decade, the development of advanced, physics-based computational peptide design tools has permitted rational design of druglike peptide macrocycles.  This webinar provides an overview of the peptide design pipelines implemented in the Rosetta and Masala software suites, and describes past work making peptides that fold into rigid binding-competent conformations that can inhibit target proteins of therapeutic interest.  It also covers ongoing work to enhance the accuracy and to expand the generality of design methods using quantum chemistry, and to raise the current ceiling of tractability with modern parallel CPU and GPU hardware, as well as with near-term quantum processors.