William Jorgensen

About

William Jorgensen is a Sterling Professor of Chemistry at Yale University and has been a member of the Yale faculty since 1990. His research interests encompass organic chemistry, theoretical chemistry, medicinal chemistry, and biophysical chemistry. His work includes simulations of organic and enzymatic reactions, computer-aided drug design, and the synthesis and development of therapeutic agents targeting infectious, inflammatory, and hyperproliferative diseases. Professor Jorgensen's approach features focused synthetic organic chemistry driven by state-of-the-art molecular design, with a focus on modeling protein-inhibitor complexes, virtual high-throughput screening, and lead-optimization guided by Monte Carlo free-energy simulations. His group has pioneered computational studies of chemistry in solution, contributing to the development and application of force fields, free-energy methods, semiempirical MO methods, and QM/MM simulations for organic and enzymatic reactions. His contributions have enabled the efficient discovery of potent anti-HIV, anti-inflammatory, and anti-cancer agents. Recognized with numerous awards and honors, including election to the American Academy of Arts and Sciences and the National Academy of Sciences, Professor Jorgensen is a leading figure in computational and theoretical chemistry.

Research topics

• Pharmacology
• Chemistry
• Biology
• Biochemistry
• Combinatorial chemistry
• Computational biology
• Stereochemistry
• Internal medicine
• Genetics
• Medicine

Selected publications

• Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations

  ACS Central Science · 2021 · 259 citations

  Senior authorCorresponding

  . Results of cell-based antiviral assays further demonstrated the potential of the compounds for treatment of COVID-19. In addition to the possible therapeutic significance, the work clearly demonstrates the power of computational chemistry for drug discovery, especially FEP-guided lead optimization.

  DOI

• Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2

  ACS Medicinal Chemistry Letters · 2020 · 220 citations

  Senior authorCorresponding

  . Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic.

  DOI

• Structure-guided design of a perampanel-derived pharmacophore targeting the SARS-CoV-2 main protease

  Structure · 2021 · 63 citations

  DOI

• OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers

  The Journal of Physical Chemistry B · 2023-12-21 · 61 citations

  article1st authorCorresponding

  The OPLS all-atom force field was updated and applied to modeling unsaturated hydrocarbons, alcohols, and ethers. Testing has included gas-phase conformational energetics, properties of pure liquids, and free energies of hydration. Monte Carlo statistical mechanics (MC) calculations were used to model 60 liquids. In addition, a robust, automated procedure was devised to compute the free energies of hydration with high precision via free-energy perturbation (FEP) calculations using double annihil…

  PublisherDOI

• The need to implement FAIR principles in biomolecular simulations

  Nature Methods · 2025-04-01 · 53 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Molecular Recognition of Proteins and Ligand Design

  NIH · $10.9M · 1990–2025

• Theoretical Bioorganic Chemistry

  NSF · $460k · 2005–2008

• Computer-Aided Design of Anti-HIV Drugs

  NIH · $7.8M · 1999–2024

Frequent coauthors

• Julian Tirado‐Rives

  Yale University

  140 shared

• Alanna Schepartz

  Arc Research Institute

  91 shared

• Scott J. Miller

  NextFlex

  89 shared

• Kenneth M. Merz

  Michigan State University

  87 shared

• Courtney C. Aldrich

  University of Minnesota System

  85 shared

• Harry A. Atwater

  California Institute of Technology

  85 shared

• Jillian M. Buriak

  University of Alberta

  85 shared

• William B. Tolman

  Washington University in St. Louis

  85 shared

Education

• Ph. D.

  Harvard University

  1975

• A. B.

  Princeton University

  1970

Awards & honors

• A. C. Cope Scholar Award (1990)
• Fellow, American Association for the Advancement of Science…
• ACS Award for Computers in Chemical and Pharmaceutical Resea…
• Sato International Award (2004)
• ISQBP Award in Computational Biology (2004)

Similar researchers at Yale University

• Jon Ellmanh-111
• Patrick Hollandh-92
• Mark Johnsonh-85