Addiction to opioid drugs causes nearly 50,000 deaths a year in the United States—and has become a major public health crisis. One solution is pharmacological: to develop an alternative to opioid medications that can relieve pain without the high risks of addiction and fatal overdoses. “That’s our goal,” says Vsevolod Katritch, Ph.D., Assistant Professor of Biological Sciences and Chemistry at the University of Southern California (USC). As an affiliated faculty member with USC’s interdisciplinary Michelson Center for Convergence Biosciences and the Center for Drug Discovery and Development, Katritch runs a lab that uses bioinformatics and molecular modeling to understand the structure and function of G protein-coupled receptors, which mediate many of the human body’s responses to external stimuli. Nilkanth Patel, a Ph.D. candidate in Katritch’s lab, explains that “you can think of opioid drugs as keys, which can selectively open or block proteins in our brain called opioid receptors. Basically, we want to find and design better keys—in this case opening the receptor that relieves pain, while blocking another that is associated with addiction.” By searching for other chemical compounds that can link to those receptors, Katritch and his team hope to discover a new generation of drugs that can become a safer alternative to opiods.
Developing new drugs is a complex, time-consuming process that can take as long as ten years and cost millions of dollars. Before pharmaceutical companies can even begin trials, research chemists need to find viable drug candidates, or ligands that bind to a specific receptor protein. Katritch’s lab uses Virtual Ligand Screening to test a vast library of possible chemical compounds by modelling each one through thousands of possible orientations into the binding pocket to find a matching protein receptor—like fitting pieces of a 3D jigsaw puzzle together. “Computation and computer-assisted design on a large scale are changing the paradigm for drug discovery,” Katritch says. His library contains over half a billion virtual compounds now and he expects that number to grow to ten billion in the near future. To analyze this vast amount of data, Katritch’s lab turned to Onix, a leading cloud services solutions provider, and Google Cloud (Google Cloud).