(135e) Invited Speaker: Toward Computer-Made Antibiotics

Machines
hold the potential to replace humans in many societal endeavors, and drug
discovery is no exception. Antibiotic innovation has been stalled for decades,
which has coincided with an alarming increase in multidrug-resistant bacteria.
Since the beginning of the antibiotic era, the natural world has been our
greatest innovator, giving rise to nearly all antibiotics available today. As
mere observers of the vast molecular diversity produced by Earth’s organisms,
we have perfected the art of isolating novel chemistries with life-saving
antimicrobial properties. However, today we are at a crossroads as no new
molecular scaffolds have been discovered for decades. We may need to look
beyond the natural world into the virtual dimension for solutions and harness
present-day computational power to help solve the global health grand challenge
of antibiotic resistance. Computer-made drugs may enable the discovery of
unprecedented functions in biological systems and help replenish our arsenal of
effective antibiotics. Proteins
perform the cellular tasks required for life. The great variety of their
biological activity is due in part to their vast combinatorial space: 20ⁿ, n
being the number of amino acids present in any given peptide chain and 20 being
the number of natural amino acid monomer building blocks. Yet we do not have the
tools to properly engineer these diverse molecules. One approach is to start
small: I will present
foundational frameworks to computationally develop peptides, tiny proteins that
display great sequence diversity but are more amenable than larger molecules to
redesign and engineering. My
approach is to expand nature’s
repertoire to build novel synthetic peptides with extremely useful properties.