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 ever discovered |
| 2013- | Determination of X-ray crystal structures for protein-ligand complexes |
| 2015- | Report of the most potent, non-toxic inhibitors of human MIF ever discovered |
| 2020- | FEP-guided design and synthesis of SARS-CoV-2 main protease (MPro, 3CLPro) non-covalent, non-peptidic inhibitors |
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
455.
Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency..
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,
ASAP articles.
doi:10.1021/acsmedchemlett.1c00326.
454.
Indoloxytriazines as Binding Molecules for the JAK2 JH2 Pseudokinase Domain and its V617F Variant.
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.
453.
Structure-guided Design of a Perampanel-derived Pharmacophore Targeting the SARS-CoV-2 Main Protease.
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,
ASAP articles.
doi:10.1016/j.str.2021.06.002.
452.
Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations..
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.
451.
Covalent Inhibition of Wild-Type HIV-1 Reverse Transcriptase Using a Fluorosulfate Warhead..
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.
450.
Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2..
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.
449.
Explicit Representation of Cation-π Interactions in Force Fields with 1/r⁴ Non-bonded Terms..
Turupcu, A.; Tirado-Rives, J.; Jorgensen, W. L.
J. Chem. Theory Comput.
2020,
16,
7184-7194.
doi:10.1021/acs.jctc.0c00847.
448.
Structural Investigation of 2-Naphthyl Phenyl Ether Inhibitors Bound to WT and Y181C Reverse Transcriptase Highlights Key Features of the NNRTI Binding Site..
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.
447.
Targeting the TS dimer interface in bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa: Virtual screening identifies novel TS allosteric inhibitors..
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.
446.
Metadynamics as a Post-Processing Method for Virtual Screening with Application to the Pseudokinase Domain of JAK2..
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.
445.
Structure-Guided Identification of DNMT3B Inhibitors..
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.
444.
Selective JAK2 Pseudokinase Ligands with a Diaminotriazole Core..
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.
443.
Absolute Free Energy of Binding Calculations for Macrophage Migration Inhibitory Factor in Complex with a Drug-like Inhibitor..
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.
442.
Structure Activity Relationship Towards the Design of Cryptosporidium Specific Thymidylate Synthase Inhibitors..
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.
441.
Molecular and Cellular Studies Evaluating a Potent 2-Cyanoindolizine Catechol Diether NNRTI Targeting Wildtype and Y181C Mutant HIV-1 Reverse Transcriptase .
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.
440.
QM/MM Calculations for the Cl- + CH3Cl SN2 Reaction in Water Using CM5 Charges and Density Functional Theory..
Tirado-Rives, J.; Jorgensen, W. L.
J. Phys. Chem. B
2019,
123,
5713-5717. Leo Radom Festschrift.
doi:10.1021/acs.jpca.9b04121.
439.
Understanding the Structural Basis of Species Selective, Stereospecific Inhibition for Cryptosporidium and Human Thymidylate Synthase..
Czyzyk, D.J.; Valhondo, M.; Jorgensen, W. L.; Anderson, K.S.
FEBS Lett.
2019,
593,
2069-2078.
doi:10.1002/1873-3468.13474.
438.
In Vivo Anticryptosporidial Efficacy of a Prodrug Nanotherapy in a Mouse Model of Cryptosporidium Infection..
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..
437.
Structural and Pharmacological Evaluation of a Novel Non-nucleoside Reverse Transcriptase Inhibitor as a Promising Long Acting Nanoformulation for Treating HIV..
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.
436.
Robust FEP Protocols for Creating Molecules in Solution..
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.
435.
Development and Testing of the OPLS-AA/M Force Field for RNA..
Robertson, M. J.; Qian, Y.; Robinson, M. C.; Tirado-Rives, J.; Jorgensen, W.L.
J. Chem. Theory Comput
2019,
15,
Article ASAP.
doi:10.1021/acs.jctc.9b00054.
434.
Computation of Protein-Ligand Binding Free Energies using Quantum Mechanical Bespoke Force Fields..
Cole, D.; Cabeza de Vaca, I.; Jorgensen, W.L.
Med. Chem. Commun.
2019,
10,
Advanced.
doi:10.1039/C9MD00017H.
433.
Novel Allosteric Covalent Inhibitors of Bifunctional Cryptosporidium hominis TS-DHFR from Parasitic Protozoa Identified by Virtual Screening..
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.
432.
Unbinding Dynamics of Non-Nucleoside Inhibitors from HIV-1 Reverse Transcriptase..
Dodda, L. S.; Tirado-Rives, J.; Jorgensen, W.L.
J. Phys. Chem. B
2019,
123(8),
1741-1748.
doi:10.1021/acs.jpcb.8b10341.
431.
Molecular Dynamics Simulations of a Conformationally Mobile Peptide-Based Catalyst for Atroposelective Bromination..
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.
430.
Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor..
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.
For more details about the specifics of the research, please see the publications page and the research page.
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
Group Photo 2017
Group Photo 2013
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.
Dept of Chemistry, Yale University
New Haven, CT 06520-8107, USA
Phone: (203)432-6288
Fax: (203)432-6144
william.jorgensen@yale.edu
Webmaster: Aysegul Turupcu
