Abba Leffler Male • United States of America

Abba E. Leffler, Ph.D., has spent his career at the intersection of science and technology, using computational tools to uncover new opportunities in drug discovery. As a Senior Principal Scientist in the therapeutics group at Schrödinger, he works to improve early-stage research by merging computer-based modeling with biological analysis. His goal is to help identify and refine molecules that have the potential to become effective medicines. Schrödinger’s advanced computational platform enables researchers in pharmaceuticals, biotechnology, and materials science to design molecules using physics-based simulations, thereby accelerating a process that has traditionally been slow and experimental.

Dr. Leffler’s research combines chemistry, computation, and biology in a way that reflects the growing collaboration between scientific disciplines. He utilizes artificial intelligence and computational chemistry to predict molecular interactions, analyze the results, and inform laboratory validation. By integrating simulation data with biological experiments, he helps teams identify compounds that are both scientifically promising and medically relevant. Over nearly ten years at Schrödinger, he has contributed to research that connects theoretical models to practical therapeutic outcomes.

He began his academic training at Princeton University, where he earned an AB in Chemistry and a Certificate in Applied Mathematics. His outstanding performance earned him the Robert Thornton McKay Prize for physical chemistry. He went on to complete his Ph.D. in Neuroscience at the NYU School of Medicine, supported by a National Institutes of Health training grant. His studies combined an understanding of quantitative methods with a focus on how biology operates at both the molecular and system levels. This combination has continued to define his research approach.

Dr. Leffler’s published work has appeared in leading scientific 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. Among his most notable contributions is his co-authored paper, “Discovery of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 Main Protease through Computer-Aided Drug Design,” published in The Journal of Medicinal Chemistry. In this study, he and his collaborators employed computer-based design methods to identify a compound that blocks a key enzyme essential for coronavirus replication. The compound, named “compound 30,” demonstrated potent antiviral activity in cell studies and performed well in early safety and dosing tests in animals. The research showed how computational tools can expedite the development of drugs effective against multiple viral variants.

In addition to this work, Dr. Leffler has co-authored several other influential papers, 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 written chapters for textbooks and is frequently invited to present at scientific conferences.

Dr. Leffler is also an inventor, holding several patents, one of which is related to a compound currently in clinical trials for the treatment of kidney cancer. Before beginning his doctoral studies, he worked at D.E. Shaw Research, where he contributed to projects using molecular dynamics simulations and supercomputing to study biological systems. This experience helped him understand how computation can support drug design by revealing details at the atomic level.

Beyond his professional achievements, Dr. Leffler is actively involved in education and the community. He is a member of the Leadership Board of the Scharf Family Chabad House at Princeton University, which provides programs and events that strengthen student life. He has volunteered for a decade as an alum interviewer and also serves on his co-op board. Over the past fifteen years, he has given outreach talks to students and educators about science and research. In recent years, he has also participated in local discussions focused on environmental conservation and community development.

Outside the lab, Abba Leffler finds balance through running and is an active member of a local running club. He attended his 15th college reunion last year, reconnecting with fellow alums and reflecting on his journey. His father, who has dedicated more than twenty years to teaching chemistry and computer science in New York City public schools, plans to retire soon, marking the close of a meaningful career in education.