William Jorgensen
Sterling Professor of ChemistryDownloadHi-Res Photo
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Director, Division of Physical Sciences & Engineering
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Sterling Professor of Chemistry
Director, Division of Physical Sciences & Engineering
Appointments
Chemistry
ProfessorPrimary
Other Departments & Organizations
- Chemistry
- Developmental Therapeutics
- Wu Tsai Institute
- Yale Cancer Center
- Yale Ventures
- Yale-UPR Integrated HIV Basic and Clinical Sciences Initiative
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Overview
Medical Research Interests
Chemistry
ORCID
0000-0002-3993-9520
Research at a Glance
Yale Co-Authors
Frequent collaborators of William Jorgensen's published research.
Publications Timeline
A big-picture view of William Jorgensen's research output by year.
Karen Anderson, PhD
Priti Kumar, PhD
David Spiegel, MD, PhD
Jason Crawford, PhD
Pradeep Uchil, PhD
Swapnil Chandrakant Devarkar
54Publications
2,388Citations
Publications
2025
Mechanistic basis for a novel dual-function Gag-Pol dimerizer potentiating CARD8 inflammasome activation and clearance of HIV-infected cells
Hollander K, Devarkar S, Tang S, Tiwari R, Ma S, Lee W, Denn E, Wang Q, Spasov K, Robbins J, Frey K, Jorgensen W, Xiong Y, Shan L, Anderson K. Mechanistic basis for a novel dual-function Gag-Pol dimerizer potentiating CARD8 inflammasome activation and clearance of HIV-infected cells. Npj Drug Discovery 2025, 2: 22. PMID: 40904837, PMCID: PMC12401731, DOI: 10.1038/s44386-025-00025-2.Peer-Reviewed Original ResearchAltmetricConceptsNon-nucleoside reverse transcriptase inhibitorsGag-Pol dimerizationGag-PolClearance of HIV-infected cellsLatent HIV-1 reservoirHIV-1-infected cellsHIV-1 reservoirHIV-infected cellsHIV-1 proteaseReverse transcriptase inhibitorsCatechol diethersHigh-throughput screeningCell-based high-throughput screeningTranscriptase inhibitorsDimerGag-Pol polyproteinDual-functionInflammasome activationInfected cellsCARD8Trigger pyroptosisFree Energies of Solvation in Benzene and Hexafluorobenzene: Is Explicit Polarization Needed?
Jorgensen W, Tirado-Rives J. Free Energies of Solvation in Benzene and Hexafluorobenzene: Is Explicit Polarization Needed? The Journal Of Physical Chemistry B 2025, 129: 6574-6583. PMID: 40530466, DOI: 10.1021/acs.jpcb.5c02405.Peer-Reviewed Original ResearchCitationsAltmetricConceptsFree energy of solvationEnergy of solvationExplicit polarizationFree energyForce fieldMonte Carlo statistical mechanicsFree energy perturbation theoryOPLS-AA force fieldFree energy of hydrationStandard force fieldsCation-p interactionsEnergy of hydrationFree energy resultsPerfluoro solventsOPLS-AAFavorable solvationAromatic ringCation-pModeling biomolecular systemsAromatic solventsOrganic moleculesLiquid benzeneSolvationTIP4P waterHexafluorobenzeneExploring Possible Drug-Resistant Variants of SARS-CoV‑2 Main Protease (Mpro) with Noncovalent Preclinical Candidate, Mpro61
Kenneson J, Papini C, Tang S, Huynh K, Zhang C, Jorgensen W, Anderson K. Exploring Possible Drug-Resistant Variants of SARS-CoV‑2 Main Protease (Mpro) with Noncovalent Preclinical Candidate, Mpro61. ACS Bio & Med Chem Au 2025, 5: 215-226. PMID: 39990941, PMCID: PMC11843330, DOI: 10.1021/acsbiomedchemau.4c00109.Peer-Reviewed Original ResearchCitationsConceptsDrug resistance mutationsViral passaging experimentsDrug-resistant clinical isolatesCOVID infectionDrug-resistant variantsSARS-CoV-2 MClinical isolatesPassage experimentsIncreased up to 10-foldClinical useSARS-CoV-2 main proteaseWild typePreclinical candidateDouble variantInhibitorsMutationsDrug developmentInfectionNirmatrelvirMain proteaseProlonged usageMedicinal chemistry modificationsVariantsTarget-based approachPatients
2024
Prodrug nanotherapy demonstrates in vivo anticryptosporidial efficacy in a mouse model of chronic Cryptosporidium infection
Ranjan A, Czyzyk D, Martinez-Traverso G, Sadiqova A, Valhondo M, Schaefer D, Spasov K, Jorgensen W, Vishwanatha J, Riggs M, Castellanos-Gonzalez A, Anderson K. Prodrug nanotherapy demonstrates in vivo anticryptosporidial efficacy in a mouse model of chronic Cryptosporidium infection. RSC Pharmaceutics 2024, 1: 963-975. PMID: 39372445, PMCID: PMC11447440, DOI: 10.1039/d4pm00093e.Peer-Reviewed Original ResearchThe Beginnings of JCTC
Jorgensen W. The Beginnings of JCTC. Journal Of Chemical Theory And Computation 2024, 20: 7692-7693. PMID: 39315606, DOI: 10.1021/acs.jctc.4c01146.Peer-Reviewed Original ResearchAltmetricMonte Carlo simulations for free energies of hydration: Past to present
Jorgensen W. Monte Carlo simulations for free energies of hydration: Past to present. The Journal Of Chemical Physics 2024, 161: 064111. PMID: 39136662, PMCID: PMC11324328, DOI: 10.1063/5.0222659.Peer-Reviewed Original ResearchCitationsConceptsFree energy of hydrationEnergy of hydrationOrganic moleculesHydration of organic moleculesMonte Carlo statistical mechanics simulationsAtom force fieldStatistical mechanics simulationsTIP4P water modelLennard-Jones interactionsUnsigned errorForce fieldCarbon atomsLennard-JonesFree energyMechanical simulationsWater modelMoleculesMonte Carlo simulationsOptimization potentialTIP4PHydrationAtomsCarlo simulationsProof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Papini C, Ullah I, Ranjan A, Zhang S, Wu Q, Spasov K, Zhang C, Mothes W, Crawford J, Lindenbach B, Uchil P, Kumar P, Jorgensen W, Anderson K. Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320713121. PMID: 38621119, PMCID: PMC11046628, DOI: 10.1073/pnas.2320713121.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDirect-acting antiviralsSARS-CoV-2Lack of off-target effectsIn vitro pharmacological profileTreatment of patientsDevelopment of severe symptomsPharmacological propertiesDrug-drug interactionsSARS-CoV-2 infectionProof-of-concept studySARS-CoV-2 Mpro .Combination regimenImmunocompromised patientsLead compoundsSARS-CoV-2 main proteaseOral doseActive drugTreat infectionsPharmacological profileSARS-CoV-2 MPotential preclinical candidateOff-target effectsPatientsComplete recoveryCapsule formulationEnthalpies and entropies of hydration from Monte Carlo simulations
Jorgensen W. Enthalpies and entropies of hydration from Monte Carlo simulations. Physical Chemistry Chemical Physics 2024, 26: 8141-8147. PMID: 38412420, PMCID: PMC10916384, DOI: 10.1039/d4cp00297k.Peer-Reviewed Original ResearchCitationsAltmetricConceptsComputing free energies of hydrationMolecular dynamicsFree energy perturbation theoryOPLS-AA force fieldFree energy of solvationTIP4P waterEnthalpy changeFree energy of hydrationEnergy of solvationOrganic solutesComputed free energiesFree energyEnergy of hydrationVan't Hoff plotsEntropy of hydrationFree energy changeVan't Hoff approachOPLS-AASolvation processPartial molar volumesForce fieldHoff plotsGas phaseEntropic componentsExcessive hydrophobicity
2023
OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers
Jorgensen W, Ghahremanpour M, Saar A, Tirado-Rives J. OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers. The Journal Of Physical Chemistry B 2023, 128: 250-262. PMID: 38127719, DOI: 10.1021/acs.jpcb.3c06602.Peer-Reviewed Original ResearchCitationsAltmetricConceptsForce fieldStatistical mechanics calculationsUnsaturated hydrocarbonsFree energyPure liquidsFree energy perturbation calculationsStandard force fieldsAtom force fieldAverage unsigned errorOrganic moleculesMechanics calculationsBiomolecular systemsConformational energeticsHeat of vaporizationLarge moleculesKcal/Perturbation calculationsUnsigned errorAverage errorLiquidEtherExperimental dataMoleculesErrorHydrationEnsemble Geometric Deep Learning of Aqueous Solubility
Ghahremanpour M, Saar A, Tirado-Rives J, Jorgensen W. Ensemble Geometric Deep Learning of Aqueous Solubility. Journal Of Chemical Information And Modeling 2023, 63: 7338-7349. PMID: 37990484, DOI: 10.1021/acs.jcim.3c01536.Peer-Reviewed Original ResearchCitationsAltmetric
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