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:

1976-82QM studies of organic ions & ion-molecule complexes
1978- MC for liquids, OPLS force field development
1980- Solvent effects on conformational equilibria
1980-95Development 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.
1988-96Molecular 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

Festschrift Cover   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 Tetrahedron Prize for Creativity in Bioorganic and Medicinal Chemistry!!!

2015


Congratulations to Professor Jorgensen on recieving the
Joel Henry Hildebrand Award in Theoretical and Experimental Chemistry of Liquids!!!

Group picture

This award was sponsored by the Exxon Mobil Research and Engineering Company and was presented by
Dr. Thomas F. Degnan, Jr. Manager, Breakthrough and Leads Generation, Exxon Mobil Research and Engineering Company.

2012


Group picture

Group Photo 2017


Group picture

Group Photo 2013