Abba E. Leffler, Ph.D., has devoted a significant portion of his professional life to advancing early-stage drug discovery through the thoughtful application of computational and biological research. As a Senior Principal Scientist at Schrödinger, he contributes to the development of new therapeutic approaches by integrating scientific modeling with laboratory data. Schrödinger’s work centers around a physics-based computational platform that improves how scientists in pharmaceuticals, biotechnology, and materials research design and test molecules. This approach helps reduce reliance on lengthy trial-and-error methods by providing precise simulations that reveal how molecules might behave in real biological systems.
Dr. Leffler’s work is grounded in the idea that combining computation and biology can lead to faster, more accurate drug development. He focuses on using artificial intelligence and computational chemistry tools to identify new drug candidates and refine existing ones. By working across multiple disciplines, chemistry, biology, and computation, he plays a key role in developing strategies that help uncover effective therapeutic compounds. Over nearly a decade at Schrödinger, he has continued to advance research at the intersection of data science and experimental medicine.
Dr. Leffler earned his AB in Chemistry from Princeton University, where he also received a Certificate in Applied Mathematics. His academic excellence was recognized with the Robert Thornton McKay Prize for physical chemistry. He later pursued a Ph.D. in Neuroscience at the NYU School of Medicine, supported by a National Institutes of Health training grant. His combination of chemistry, mathematics, and neuroscience has shaped his ability to approach complex biological problems with both precision and creativity.
His body of research has been featured in several leading journals, including Science, The Journal of Medicinal Chemistry, The Journal of Neuroscience, ACS Medicinal Chemistry Letters, The Journal of Chemical Information and Modeling, and Proceedings of the National Academy of Sciences. One of his most impactful papers, published in The Journal of Medicinal Chemistry, is titled “Discovery of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 Main Protease through Computer-Aided Drug Design.” In that study, Dr. Leffler and his collaborators used computational modeling to design a compound that effectively blocks a viral enzyme necessary for coronavirus replication. The resulting molecule, known as “compound 30,” demonstrated strong antiviral effects in cell tests and performed well in early safety and dosing studies in animals. The research suggests that the compound has the potential to become part of a new generation of antiviral drugs capable of targeting a range of coronaviruses.
Beyond this work, Dr. Leffler has co-authored several critical studies, including “Exploiting Solvent Exposed Salt-Bridge Interaction for the Discovery of Potent Inhibitors of SOS1 Using Free-Energy Perturbation Simulations,” “How Does a Small Molecule Bind at a Cryptic Binding Site?”, and “AutoDesigner, a De Novo Design Algorithm for Rapidly Exploring Large Chemical Space for Lead Optimization: Application to the Design and Synthesis of D-Amino Acid Oxidase Inhibitors.” He has contributed chapters to textbooks and regularly participates in scientific discussions and conferences.
His inventive contributions include multiple patents, one of which is for a compound currently being tested in clinical trials for the treatment of kidney cancer. Before beginning his doctoral studies, Dr. Leffler worked at D.E. Shaw Research, a firm renowned for its computational work, which utilizes supercomputers and molecular dynamics simulations to study biological systems in great detail. His experience there helped him build a strong technical foundation that continues to inform his research.
Outside of his scientific career, Dr. Leffler remains deeply involved in community and educational initiatives. He supports Princeton University through his role on the Leadership Board of the Scharf Family Chabad House, which organizes programs that bring students together in a welcoming environment. He has volunteered as an alum interviewer for ten years and is an active member of his co-op board. For more than fifteen years, he has given outreach talks at universities and high schools, encouraging younger audiences to explore science and discovery. In recent years, he has participated in local political meetings to learn more about how communities can support the conservation of trees and wildlife.
When not engaged in research or community work, Abba Leffler enjoys running and participates in a local running club. Last year, he returned to Princeton for his 15th college reunion. His father, who has taught chemistry and computer science in New York City public schools for over twenty years, will retire at the end of the year, bringing to a close a long and dedicated career in education.
