William L. Jorgensen (born October 5, 1949) is an American chemist specializing in computational and medicinal chemistry, serving as the Sterling Professor of Chemistry at Yale University since 2009, having joined the Yale faculty in 1990. He is renowned for pioneering computational studies of organic and biomolecular systems in aqueous solution, including the development of the influential OPLS (Optimized Potentials for Liquid Simulations) force fields and TIPnP water models that have enabled widespread modeling of biomolecular processes since the 1980s. Jorgensen's research integrates free-energy perturbation methods for studying reaction mechanisms, host-guest binding, and equilibria; mixed quantum and molecular mechanics (QM/MM) simulations for organic and enzymatic reactions; and computer-aided drug design targeting proteins involved in infectious, inflammatory, and hyperproliferative diseases. His approaches have facilitated the discovery of potent inhibitors, such as anti-HIV agents targeting reverse transcriptase and CXCR4, anti-inflammatory compounds against MIF and JAK2 kinase, and anti-cancer drugs for parasitic enzymes like TS-DHFR. He has also developed key molecular modeling software, including BOSS for simulations, MCPRO for protein folding, and BOMB for generating combinatorial libraries in virtual screening. Educated with an A.B. from Princeton University in 1970 and a Ph.D. from Harvard University in 1975, Jorgensen previously held positions at Purdue University before joining Yale. He served as Director of Yale's Division of Physical Sciences & Engineering from 2009 to 2012 and was elected to the National Academy of Sciences in 2011 for his contributions to chemistry and computational biology. Among his numerous honors are the ACS Award for Computers in Chemical and Pharmaceutical Research (1998), the Joel H. Hildebrand Award in the Theoretical and Experimental Chemistry of Liquids (2012), the Tetrahedron Prize (2015), and the Arthur C. Cope Award (2024).
Early life and education
Early life William L. Jorgensen was born on October 5, 1949, in New York City. His father, Axel V. Jorgensen (1912–1996), had immigrated to the United States from Denmark in 1935 and worked his entire career as an engineer for the Danish firm F. L. Smidth, primarily in midtown Manhattan; he was multilingual, speaking six languages, and earned a B.A. in economics from New York University while attending night classes. Jorgensen's mother, Alice Lane Jorgensen (1911–1990), grew up in Spokane, Washington, and obtained B.A. and M.A. degrees from the University of Montana and Columbia Teachers College, respectively; many of her relatives had been homesteaders in Montana during the 1920s. He had one sibling, an older brother named Lane, who later graduated from Lehigh University as an engineer. The family environment, influenced by his parents' professional pursuits and intellectual discussions, fostered an early curiosity in Jorgensen about scientific and technical subjects. In 1950, the family relocated from Manhattan to Port Washington on Long Island, where Jorgensen attended St. Peter of Alcantara School through fifth grade. Following his brother's departure for college in 1960, they moved again to Sherman, Connecticut, and he completed sixth through eighth grade at the local public school, graduating in 1963 as part of a class of 12 students. During his childhood in these settings, Jorgensen's interest in science was notably sparked in the early 1960s when his parents gifted him a Gilbert Chemistry Set, enabling hands-on experiments with readily available chemicals from local stores, such as potassium nitrate. He described himself as an adventurous child and directed his path toward chemistry without a singular, predefined ambition.
Education William L. Jorgensen earned an A.B. degree in chemistry from Princeton University in 1970, completing the program in three years thanks to advanced placement credits that allowed him to accelerate his studies. He initially enrolled in the chemical engineering sequence but switched to chemistry after his first semester, taking key courses in physical chemistry under Professor Walter J. Kauzmann, organic chemistry with Professors Paul von Ragué Schleyer and Ted Taylor, and inorganic chemistry with Neil Bartlett. During his undergraduate years, Jorgensen joined Professor Leland C. Allen's research group, where he gained early exposure to computational methods through ab initio quantum mechanics and semiempirical molecular orbital calculations using programs like CNDO and NDDO on IBM computers; this work led to his first publication in the Journal of the American Chemical Society in 1970, evaluating these methods for hydrocarbons. Jorgensen pursued graduate studies at Harvard University, earning a Ph.D. in chemical physics in 1975 under the advisory of Nobel laureate Elias J. Corey. His doctoral thesis focused on computational aspects of organic chemistry, particularly the development of the LHASA (Logic and Heuristics Applied to Synthetic Analysis) program for computer-assisted retrosynthetic analysis, which built on earlier systems like OCSS and included modules for disconnections, functional group interchanges, symmetry recognition, and synthetic strategies. This work, conducted initially in assembly language on a DEC PDP-1 and later in FORTRAN on a PDP-10, resulted in two publications in the Journal of the American Chemical Society. Throughout his graduate studies, Jorgensen maintained interests in quantum mechanics, modifying CNDO codes for MINDO and extended Hückel theory, and collaborating on molecular orbital calculations and 3D plotting techniques, which further honed his computational expertise. His thesis committee included Corey, William Lipscomb, and R. B. Woodward.
Professional career
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