Welcome to the Jorgensen Lab
For many years, the Jorgensen Research Group has been at the forefront of computational chemistry and molecular design. Below is an outline of our progress:
| 1976-82 | QM studies of organic ions & ion-molecule complexes |
|---|---|
| 1978- | MC for liquids, OPLS force field development |
| 1980- | Solvent effects on conformational equilibria |
| 1980-95 | Development of CAMEO for prediction of products of organic reactions |
| 1983 | TIP3P & TIP4P water models |
| 1984 | Free-energy profiles for SN2 reactions in solution |
| 1985 | 1st FEP calculation: CH3CH3 --> CH3OH in water |
| 1985- | FEP for reactions in solution (QM + MM), ΔGhyd, ion-pairing, pKas, log P, hydrophobic effects, etc. |
| 1988-96 | Molecular recognition/organic host-guest complexes |
| 1989 | Secondary electrostatic effects for G-C, A-T, etc. |
| 1987- | MD and MC for proteins, denaturation, folding, enzymatic rxns |
| 1996- | FEP/MC for protein-ligand binding |
| 1997- | Full QM/MM for organic & enzymatic reactions |
| 2000- | Structure-based drug design, ADME predictions |
| 2001- | Semiempirical molecular orbital method development |
| 2003- | FEP-guided design and synthesis of enzyme inhibitors |
| 2009- | Discovery of MIF antagonists and agonists |
| 2011- | Report of the most potent, non-toxic anti-HIV agents |
| 2013- | Determination of X-ray crystal structures for protein-ligand complexes |
| 2015- | Report of the most potent, non-toxic inhibitors of human MIF |
| 2017- | Discovery of selective binding molecules for the pseudokinase domain of JAK2 |
| 2020- | FEP-guided design and synthesis of SARS-CoV-2 main protease (MPro, 3CLPro) non-covalent, non-peptidic inhibitors |
News
Congratulations to Professor Jorgensen on being awarded the "To recognize outstanding achievement in the field of organic chemistry, the significance
of which click on the following links to read the announcement 2023
Congratulations to Professor Jorgensen on being awarded the note: click on the image below and scroll down to see the inteview
2021
Congratulations to Professor Jorgensen on being awarded the
2015
Congratulations to Professor Jorgensen on recieving the This award was sponsored by the Exxon Mobil Research and Engineering Company and was presented by 2012
470.
Proof-of-Concept Studies with a Computationally Designed Mpro Inhibitor as a Synergistic Combination Regimen Alternative to Paxlovid..
469.
Enthalpies and Entropies of Hydration From Monte Carlo Simulations..
468.
OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers.
467.
Ensemble Geometric Deep Learning of Aqueous Solubility.
466.
A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening.
465.
Assessing Metadynamics and Docking for Absolute Binding Free Energy Calculations Using Severe Acute Respiratory Syndrome Coronavirus 2 Main Protease Inhibitors.
464.
Covalent and Noncovalent Strategies for Targeting Lys102 in HIV-1 Reverse Transcriptase.
463.
Exploring Novel HIV-1 Reverse Transcriptase Inhibitors with Drug Resistant Mutants: A Double Mutant Surprise.
462.
Computation of Absolute Binding Free Energies for Noncovalent Inhibitors with SARS-CoV-2 Main Protease.
461.
Progress on the Pharmacological Targeting of Janus Pseudokinases.
460.
Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase.
459.
Covalent Modification of the JH2 Domain of Janus Kinase 2.
458.
Refinement of the Optimized Potentials for Liquid Simulations Force Field for Thermodynamics and Dynamics of Liquid Alkanes..
457.
Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands..
456.
Conversion of a False Virtual Screen Hit into Selective JAK2 JH2 Domain Binders Using Convergent Design Strategies..
455.
Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency..
454.
Indoloxytriazines as Binding Molecules for the JAK2 JH2 Pseudokinase Domain and its V617F Variant.
453.
Structure-guided Design of a Perampanel-derived Pharmacophore Targeting the SARS-CoV-2 Main Protease.
452.
Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations..
451.
Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead..
450.
Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2..
449.
Explicit Representation of Cation-π Interactions in Force Fields with 1/r⁴ Non-bonded Terms..
448.
Structural Investigation of 2-Naphthyl Phenyl Ether Inhibitors Bound to WT and Y181C Reverse Transcriptase Highlights Key Features of the NNRTI Binding Site..
447.
Targeting the TS dimer interface in bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa: Virtual screening identifies novel TS allosteric inhibitors..
446.
Metadynamics as a Post-Processing Method for Virtual Screening with Application to the Pseudokinase Domain of JAK2..
445.
Structure-Guided Identification of DNMT3B Inhibitors..
444.
Selective JAK2 Pseudokinase Ligands with a Diaminotriazole Core..
443.
Absolute Free Energy of Binding Calculations for Macrophage Migration Inhibitory Factor in Complex with a Drug-like Inhibitor..
442.
Structure Activity Relationship Towards the Design of Cryptosporidium Specific Thymidylate Synthase Inhibitors..
441.
Molecular and Cellular Studies Evaluating a Potent 2-Cyanoindolizine Catechol Diether NNRTI Targeting Wildtype and Y181C Mutant HIV-1 Reverse Transcriptase .
440.
QM/MM Calculations for the Cl- + CH3Cl SN2 Reaction in Water Using CM5 Charges and Density Functional Theory..
439.
Understanding the Structural Basis of Species Selective, Stereospecific Inhibition for Cryptosporidium and Human Thymidylate Synthase..
438.
In Vivo Anticryptosporidial Efficacy of a Prodrug Nanotherapy in a Mouse Model of Cryptosporidium Infection..
437.
Structural and Pharmacological Evaluation of a Novel Non-nucleoside Reverse Transcriptase Inhibitor as a Promising Long Acting Nanoformulation for Treating HIV..
436.
Robust FEP Protocols for Creating Molecules in Solution..
435.
Development and Testing of the OPLS-AA/M Force Field for RNA..
434.
Computation of Protein-Ligand Binding Free Energies using Quantum Mechanical Bespoke Force Fields..
433.
Novel Allosteric Covalent Inhibitors of Bifunctional Cryptosporidium hominis TS-DHFR from Parasitic Protozoa Identified by Virtual Screening..
432.
Unbinding Dynamics of Non-Nucleoside Inhibitors from HIV-1 Reverse Transcriptase..
431.
Molecular Dynamics Simulations of a Conformationally Mobile Peptide-Based Catalyst for Atroposelective Bromination..
430.
Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor..
For more details about the specifics of the research, please see the publications page and the research page.
Group Photo 2019
Group Photo 2013
2024 ACS Arthur C. Cope Award!!!
has become apparent within the five years preceding the year if which the award will be presented".
from the
American Chemical Society
and from Yale News
2021 Citation Laureate Award!!!
2015 Tetrahedron Prize for Creativity in Bioorganic and Medicinal Chemistry!!!
Joel Henry Hildebrand Award in Theoretical and Experimental Chemistry of Liquids!!!
Dr. Thomas F. Degnan, Jr. Manager, Breakthrough and Leads Generation, Exxon Mobil Research and Engineering Company.
William L. Jorgensen Festschrift
The Journal of Physical Chemistry B
January 22, 2015 ,
Volume 119, Issue 3 , Pages 621-1232.
Festschrift Preface includes:
393. Tribute to William L. Jorgensen.
Gao, J.; Orozco, M.; Peishoff, C. E.
J. Phys. Chem. B
2015 , 119 , 621-623. doi:10.1021/jp511519w .
394. Autobiography of William L. Jorgensen: Scientific History and Recollections.
Jorgensen, W. L.
J. Phys. Chem. B
2015 , 119 , 624-632. doi:10.1021/jp510442j .
395. Group Members of William L. Jorgensen (1975-2014).
J. Phys. Chem. B
2015 , 119 , 633-634. doi:10.1021/jp5104406 .
396. Abbreviated Curriculum Vitae of William L. Jorgensen.
J. Phys. Chem. B
2015 , 119 , 635-636. doi:10.1021/jp510441r .
Newest Publications
Papini, C.; Ullah, I.; Ranjan, A. P.; Zhang, S.'Wu, Q.; Spasov, K. A.; Zhang, C.; Mothes, W.; Crawford, J. M.; Lindenbach, B. D.; Uchil. P. D.; Kumar, P.; Jorgensen, W. L.; Anderson, K. S.
Proc. Nat. Acad. Sci. USA
2024,
121,
e2320713121.
doi:10.1073/pnas.232071312.
Jorgensen, W. L.
Phys. Chem. Chem. Phys.
2024,
26,
8141-8147.
doi:10.1039/D4CP00297K.
Jorgensen, W. L.; Ghahremanpour, M. M.; Saar, A.; Tirado-Rives, J.
J. Phys. Chem. B
2023,
127,
250-262.
doi:10.1021/acs.jpcb.3c06602.
Ghahremanpour, M. M.; Saar, A.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Inf. Model.
2023,
63,
7338-7349.
doi:10.1021/acs.jcim.3c01536.
Fisher, C. R.; Medie, F. M.; Luu, R. J.; Gaibler, R. B.; Mulhern, T. J.; Miller, C. R.; Zhang, C. J.; Rubio, L. D.; Marr, E. E.; Vijayakumar, V.; Gabriel, E. P; Lopez Quezada, L.; Zhang, C.-H.; Anderson, K. S. Jorgensen, W. L.; Alladina, J. W.;cMedoff, B. D.; Borenstein, J. T.; Gard, A. L.
Cells
2023,
12,
2639.
doi:10.3390/cells12222639.
Saar, A.; Ghahremanpour, M. M.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Inf. Model.
2023,
63,
7210-7218.
doi:10.1021/acs.jcim.3c01453.
Prucha, G. R.; Henry, S.; Hollander, K.; Carter, Z.; J.; Spasov, K. A.; Jorgensen, W. L.; Anderson, K, S.
Eur. J. Med. Chem.
2023,
262,
115984.
doi:10.1016/j.ejmech.2023.115894.
Hollander, K,; Chan, A. H.; Frey, K. M.; Hunker, O.; Ippolito, J. A.; Spasov, K. A.; Yeh, Y. J.; Jorgensen, W. L.; Ho, Y.; Anderson, K. S.
Protein Sci.
2023,
32,
e4814.
doi:10.1002/pro.4814.
Ghahremanpour, M. M.; Saar, A.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Inf. Model.
2023,
63,
5309-5318.
doi:10.1021/acs.jcim.3c00874.
Henry, S. P.; Jorgensen, W. L.
J Med. Chem.
2023,
66,
10959-10990.
doi:10.1021/acs.jmedchem.3c00926.
Carter, Z. J.; Hollander, K, A.; Spasov, K. A.; Anderson, K, S,; Jorgensen, W. L.
Bioorg. Med. Chem. Lett.
2023,
84,
129216.
doi:10.1016/j.bmcl.2023.129216.
Henry, S. P.; Liosi, M-E.; Ippolito, J. A.; Menges, F.; Newton, A. S.; Schlessinger, J,; Jorgensen, W. L.
ACS Med. Chem. Lett.
2022,
13,
1819-1826.
doi:10.1021/acsmedchemlett.2c00414.
Ghahremanpour, M. M.; Tirado-Rives, J.; Jorgensen, W. L.
J. Phys. Chem. B
2022,
126,
5896-5907.
doi:10.1021/acs.jpcb.2c03686.
Liosi, M.-E.; Ippolito, J. A.; Henry, S. P. Krimmer, S. G.; Newton, A. S.; Cutrona, K. J.; Olivarez, R. A.; Mohanty, J.; Schlessinger, J.; Jorgensen, W. L.
J. Med. Chem.
2022,
13,
819-826.
doi:10.1021/acs.jmedchem.2c00283.
Henry, S. P.; Liosi, M-E.; Ippolito, J. A.; Cutrona, K. J.; Krimmer, S. G.; Newton, A. S.; Schlessinger, J.; Jorgensen, W. L.
ACS Med. Chem. Lett.
2022,
12,
819-826.
doi:10.1021/acsmedchemlett.2c00051.
Zhang, C.-H.; Spasov, K. A.; Reilly, R. A.; Hollander, K. A.; Stone, E. A.; Ippolito, J. A.; Liosi, M.-E.; Deshmukh, M. G.; Tirado-Rives, J.; Zhang, S.; Liang, Z.; Miller, S. J.; Isaacs, F.; Lindenbach, B. D.; Anderson, K. S.; Jorgensen, W. L.
ACS Med. Chem. Lett.
2021,
12,
1325-1332.
doi:10.1021/acsmedchemlett.1c00326.
Newton, A. S.; Liosi, M.-E.; Henry, S. P.; Deiana, L.; Faver, J. C.; Krimmer, S. G.; Puleo, D. E.; Schlessinger, J.; Jorgensen, W. L.
Tetrahedron Lett.
2021,
153248.
doi:10.1016/j.tetlet.2021.153248.
Deshmukh, M. G.; Ippolito, J. A.; Zhang, C.-H.; Stone, E. A.; Reilly, R. A.; Miller, S. J.; Jorgensen, W. L.; Anderson, K. S.;
Structure
2021,
29,
823-833.
doi:10.1016/j.str.2021.06.002.
Zhang, C-H.; Stone, E. A.; Deshmukh, M.; Ippolito, J. A.; Ghahremanpour, M. M.; Tirado-Rives, J.; Spasov, K. A.; Zhang, S.; Takeo, Y.; Kudalkar, S. N.; Liang, Z.; Isaacs, F.; Lindenbach, B.; Miller, S. J.; Anderson, K. S.; Jorgensen, W. L.
ACS Cent. Sci.
2021,
7,
467-475.
doi:10.1021/acscentsci.1c00039.
Ippolito, J. A.; Niu, H.; Bertoletti, N.; Carter, Z. J.; Jin, S.; Spasov, K. A.; Cisneros, J. A.; Valhondo, M.; Cutrona, K. J.; Anderson, K. S.; Jorgensen, W. L.
ACS Med. Chem. Lett.
2021,
12,
249-255.
doi:10.1021/acsmedchemlett.0c00612.
Ghahremanpour, M.; Tirado-Rives, J.; Deshmukh, M.; Ippolito, J. A.; Zhang, C.-H.; Cabeza de Vaca, I.; Liosi, M.-E.; Anderson, K. S.; Jorgensen, W. L.
ACS Med. Chem. Lett.
2020,
11,
2526-2533.
doi:10.1021/acsmedchemlett.0c00521.
Turupcu, A.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Theory Comput.
2020,
16,
7184-7194.
doi:10.1021/acs.jctc.0c00847.
Duong, V. N.; Ippolito, J. A.; Chan, A. H.; Lee, W.-G.; Spasov, K. S.; Jorgensen, W. L.; Anderson, K. S.
Protein Sci.
2020,
29,
1902-1910.
doi:10.1002/pro.3910.
Ruiz, V. G.; Czyzyk, D. J.; Kumar, V. P.; Jorgensen, W. L.; Anderson, K. S.
Bioorg. Med. Chem. Lett.
2020,
30,
127292.
doi:10.1016/j.bmcl.2020.127292.
Cutrona, K. J.; Newton, A. S.; Krimmer, S. G.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Info. Model.
2020,
60,
4403-4415.
doi:10.1021/acs.jcim.0c00276.
Newton, A. S.; John C. Faver, J. C.; Micevic, G.; Muthusamy, V.; Kudalkar, S. N.; Bertoletti, N.; Anderson, K. S.; Bosenberg, M. W.; Jorgensen, W. L.
ACS Med. Chem. Lett.
2020,
11,
971-976. M. Botta Memorial Issue..
doi:10.1021/acsmedchemlett.0c00011.
Liosi, M.-E.; Krimmer, S. G.; Newton, A. S.; Dawson, T. K.; Puleo, D. E.; Cutrona, K. J.; Schlessinger, J.; Jorgensen, W. L.
J. Med. Chem.
2020,
63,
5324-5340.
doi:10.1021/acs.jmedchem.0c00192.
Qian, Y.; Cabeza de Vaca, I.; Vilseck, J. Z.; Cole, D. J.; Tirado-Rives, J.; Jorgensen, W. L.
J. Phys. Chem. B
2019,
123,
8675-8685.
doi:10.1021/acs.jpcb.9b07588.
Czyzyk, D.; Valhondo, M.; Tirado-Rives, J.; Jorgensen, W. L.; Anderson, K. S.
Eur. J. Med. Chem.
2019,
183,
111673.
doi:10.1016/j.ejmech.2019.111673.
Sasaki, T.; Gannam, Z. T. K.; Kudalkar, S. N.; Frey, K. M.; Lee, W.-G.; Spasov, K. A.; Jorgensen, W. L.; Anderson, K. S.
Bioorg. Med. Chem. Lett.
2019,
29,
2182-2188.
doi:10.1016/j.bmcl.2019.06.047.
Tirado-Rives, J.; Jorgensen, W. L.
J. Phys. Chem. B
2019,
123,
5713-5717. Leo Radom Festschrift.
doi:10.1021/acs.jpca.9b04121.
Czyzyk, D.J.; Valhondo, M.; Jorgensen, W. L.; Anderson, K.S.
FEBS Lett.
2019,
593,
2069-2078.
doi:10.1002/1873-3468.13474.
Ranjan, A.P.; Czyzyk, D.J.; Martinez-Traverso, G.; Valhondo, M.; Jorgensen, W.L; Vishwanatha, J.K.; Castellanos-Gonzalez, A.; Anderson, K.S.
Antimicrob. Agents Chemother.
2019,
00,
0000-0000. Submitted..
Kudalkar, S. N.; Ullah, I.; Bertoletti, N.; Mandl, H.; Cisneros, J. A.; Beloor, J.; Chan, A. H.; Saltzman, W. M.; Jorgensen, W. L.; Kumar, P.; Anderson, K. S.
Antiviral Res.
2019,
167,
110-116. PMID: 31034849.
doi:10.1016/j.antiviral.2019.04.010.
Cabeza de Vaca, I.; Zarzuela, R.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Theory Comput.
2019,
15,
3941-3948.
doi:10.1021/acs.jctc.9b00213.
Robertson, M. J.; Qian, Y.; Robinson, M. C.; Tirado-Rives, J.; Jorgensen, W.L.
J. Chem. Theory Comput
2019,
15,
2734-2742.
doi:10.1021/acs.jctc.9b00054.
Cole, D.; Cabeza de Vaca, I.; Jorgensen, W.L.
Med. Chem. Commun.
2019,
10,
Advanced.
doi:10.1039/C9MD00017H.
Ruiz, V.; Czyzyk, D. J.; Valhondo, M.; Jorgensen, W. L.; Anderson, K. S.
Bioorg. Med. Chem. Lett.
2019,
29,
1413-1418. PMID: 30929953.
doi:10.1016/j.bmcl.2019.03.022.
Dodda, L. S.; Tirado-Rives, J.; Jorgensen, W.L.
J. Phys. Chem. B
2019,
123(8),
1741-1748.
doi:10.1021/acs.jpcb.8b10341.
Yan, X. C.; Metrano, A. J.; Robertson, M. J.; Abascal, N. C.; Tirado-Rives, J.; Miller, S. J.; Jorgensen, W.L.
ACS Catalysis
2018,
8(11),
9968-9979.
doi:10.1021/acscatal.8b03563.
Trivedi-Parmar, V.; Robertson, M. J.; Cisneros, J. A.; Krimmer, S. G.; Jorgensen, W.L.
ChemMedChem
2018,
13(11),
1092-1097.
doi:10.1002/cmdc.201800158.
Pictures
Dept of Chemistry, Yale University
New Haven, CT 06520-8107, USA
Phone: (203)432-6288
Fax: (203)432-6144
william.jorgensen@yale.edu
Webmaster: Julian Tirado-Rives
