Dr. Abba E. Leffler, Ph.D., is a Senior Principal Scientist in the therapeutics group at Schrödinger, where he plays a leading role in early-stage drug discovery. Schrödinger is widely recognized for its physics-based computational platform, which allows scientists in biotechnology, pharmaceutical research, and materials science to model molecular behavior with remarkable precision. This approach significantly reduces reliance on traditional laboratory work, enabling researchers to explore chemical space more profoundly and more rapidly than would otherwise be possible.

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Within this environment, Abba Leffler’s work stands at the intersection of chemistry, computation, and biology. He focuses on understanding the molecular mechanisms underlying disease and then applies computational tools, such as free-energy perturbation simulations and AI-driven modeling, to design promising therapeutic compounds. His expertise allows him to bridge the gap between complex biological systems and computationally generated insights, ultimately contributing to more efficient and accurate drug discovery.

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With nearly a decade at Schrödinger, Dr. Leffler has become an integral part of the company’s mission to modernize the discovery of new medicines. His contributions help accelerate the transition from concept to candidate, improving the likelihood of identifying molecules that can advance successfully into experimental testing.

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Academic Journey and Early Scientific Achievement

Dr. Leffler’s foundations in scientific inquiry were established during his undergraduate years at Princeton University, where he earned an AB in Chemistry along with a Certificate in Applied Mathematics. His academic excellence was recognized with the Robert Thornton McKay Prize for Physical Chemistry, awarded to students demonstrating outstanding achievement in the field.

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He continued his scientific training at the NYU School of Medicine, completing a Ph.D. in Neuroscience. His doctoral work was supported by a prestigious National Institutes of Health training grant, underscoring his potential as a researcher and his commitment to advancing scientific understanding. The interdisciplinary nature of his education, spanning chemistry, mathematics, and neuroscience, prepared him to tackle the multifaceted challenges of therapeutic discovery.

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A Strong Publication Record and Scientific Contributions

Abba Leffler has contributed to numerous highly respected scientific journals, including Science, The Journal of Medicinal Chemistry, ACS Medicinal Chemistry Letters, The Journal of Neuroscience, The Journal of Chemical Information and Modeling, and PNAS. His publications reflect a career dedicated to discovering new therapeutic strategies and deepening understanding of molecular interactions.

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One of his most recent and notable contributions is a publication in The Journal of Medicinal Chemistry, where he and his collaborators describe the discovery of potent noncovalent inhibitors of the SARS-CoV-2 main protease. Using advanced computer-aided drug design tools, the team identified compounds that can block a key viral enzyme essential for coronavirus replication. Their lead molecule, “compound 30,” not only demonstrated antiviral activity in laboratory studies but also showed effectiveness against multiple coronavirus variants, including the Omicron variant. Early safety and dosing studies in animal models indicated favorable properties, positioning the compound as a potential candidate for future clinical development. If further testing confirms its promise, it may become part of a new generation of antiviral therapies designed to help society respond more rapidly to emerging viral threats.

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Dr. Leffler’s additional work includes research on cryptic binding sites, solvent-exposed molecular interactions, and the development of computational design tools such as AutoDesigner. These studies continue to influence how scientists conceptualize molecular interactions in drug discovery.

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Patents, Previous Experience, and Innovation

Beyond publications, Dr. Leffler is an inventor on multiple patents, including one for a compound currently in clinical trials for kidney cancer. Before pursuing his doctorate, he worked at D.E. Shaw Research, a leader in computational modeling, where he contributed to efforts involving custom supercomputers, molecular dynamics simulations, and machine learning applied to biological systems.

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Commitment to Community and Personal Interests

Abba Leffler’s impact extends beyond his scientific work. He supports Princeton University as part of the Leadership Board for the Scharf Family Chabad House, helps foster Jewish student life, and has served as an alumni interviewer for ten years. He has also volunteered on his co-op board and has given outreach talks at universities and high schools for more than fifteen years.

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In recent years, he has become increasingly involved in local political meetings to better understand how communities can support environmental conservation. Outside of professional and volunteer commitments, he enjoys running and is an active member of a running club. He also recently celebrated his 15th college reunion. His family includes his father, who is retiring after more than twenty years as a New York City public school teacher specializing in chemistry and computer science.