William L. Jorgensen
Yale University
H-index: 133
North America-United States
Description
William L. Jorgensen, With an exceptional h-index of 133 and a recent h-index of 59 (since 2020), a distinguished researcher at Yale University, specializes in the field of Chemistry, Biochemistry.
His recent articles reflect a diverse array of research interests and contributions to the field:
Enthalpies and entropies of hydration from Monte Carlo simulations
Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase
Ensemble Geometric Deep Learning of Aqueous Solubility
Pyrazole-Containing Macrophage Migration Inhibitory Factor Inhibitors
A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening
OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers
MIF modulators
Professor Information
University | Yale University |
---|---|
Position | Sterling Professor of Chemistry |
Citations(all) | 139091 |
Citations(since 2020) | 41214 |
Cited By | 114692 |
hIndex(all) | 133 |
hIndex(since 2020) | 59 |
i10Index(all) | 453 |
i10Index(since 2020) | 244 |
University Profile Page | Yale University |
Research & Interests List
Chemistry
Biochemistry
Top articles of William L. Jorgensen
Enthalpies and entropies of hydration from Monte Carlo simulations
The changes in free energy, enthalpy, and entropy for transfer of a solute from the gas phase into solution are the fundamental thermodynamic quantities that characterize the solvation process. Owing to the development of methods based on free-energy perturbation theory, computation of free energies of solvation has become routine in conjunction with Monte Carlo (MC) statistical mechanics and molecular dynamics (MD) simulations. Computation of the enthalpy change and by inference the entropy change is more challenging. Two methods are considered in this work corresponding to direct averaging for the solvent and solution and to computing the temperature derivative of the free energy in the van’t Hoff approach. The application is for neutral organic solutes in TIP4P water using long MC simulations to improve precision. Definitive results are also provided for pure TIP4P water. While the uncertainty in …
Authors
William L Jorgensen
Journal
Physical Chemistry Chemical Physics
Published Date
2024
Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug. Serious drug–drug interactions can occur with Paxlovid for patients who are also taking other medications metabolized by CYP4503A4, particularly transplant or otherwise immunocompromised patients who are most at risk for SARS-CoV-2 infection and the development of severe symptoms. Developing an alternative antiviral with improved pharmacological properties is critical for treatment of these …
Authors
Christina Papini,Irfan Ullah,Amalendu P Ranjan,Shuo Zhang,Qihao Wu,Krasimir A Spasov,Chunhui Zhang,Walther Mothes,Jason M Crawford,Brett D Lindenbach,Pradeep D Uchil,Priti Kumar,William L Jorgensen,Karen S Anderson
Journal
Proceedings of the National Academy of Sciences
Published Date
2024/4/23
Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase
We report non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) using a biphenylmethyloxazole pharmacophore. A crystal structure of benzyloxazole 1 was obtained and suggested the potential viability of biphenyl analogues. In particular, 6a, 6b, and 7 turned out to be potent NNRTIs with low-nanomolar activity in enzyme inhibition and infected T-cell assays, and with low cytotoxicity. Though modeling further suggested that analogues with fluorosulfate and epoxide warheads might provide covalent modification of Tyr188, synthesis and testing did not find evidence for this outcome.
Authors
Zachary J Carter,Klarissa Hollander,Krasimir A Spasov,Karen S Anderson,William L Jorgensen
Journal
Bioorganic & Medicinal Chemistry Letters
Published Date
2023/3/15
Ensemble Geometric Deep Learning of Aqueous Solubility
Geometric deep learning is one of the main workhorses for harnessing the power of big data to predict molecular properties such as aqueous solubility, which is key to the pharmacokinetic improvement of drug candidates. Two ensembles of graph neural network architectures were built, one based on spectral convolution and the other on spatial convolution. The pretrained models, denoted respectively as SolNet-GCN and SolNet-GAT, significantly outperformed the existing neural networks benchmarked on a validation set of 207 molecules. The SolNet-GCN model demonstrated the best performance on both the training and validation sets, with RMSE values of 0.53 and 0.72 log molar unit and Pearson r2 values of 0.95 and 0.75, respectively. Further, the ranking power of the SolNet models agreed well with a QM-based thermodynamic cycle approach at the PBE-vdW level of theory on a series of benzophenylurea …
Authors
Mohammad M Ghahremanpour,Anastasia Saar,Julian Tirado-Rives,William L Jorgensen
Journal
Journal of Chemical Information and Modeling
Published Date
2023/11/22
Pyrazole-Containing Macrophage Migration Inhibitory Factor Inhibitors
SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1, 4-dien-1-yl (diphenyl) phosphane; dichloromethane; dichloropalladium; iron (2+) Chemical compound [Fe+2]. ClCCl. Cl [Pd] Cl. C1= C [CH-] C (P (C= 2C= CC= CC= 2) C= 2C= CC= CC= 2)= C1. C1= C [CH-] C (P (C= 2C= CC= CC= 2) C= 2C= CC= CC= 2)= C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 29
Published Date
2023/2/23
A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening
COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system.
Authors
Christine R Fisher,Felix Mba Medie,Rebeccah J Luu,Robert B Gaibler,Thomas J Mulhern,Caitlin R Miller,Chelsea J Zhang,Logan D Rubio,Elizabeth E Marr,Vidhya Vijayakumar,Elizabeth P Gabriel,Landys Lopez Quezada,Chun-Hui Zhang,Karen S Anderson,William L Jorgensen,Jehan W Alladina,Benjamin D Medoff,Jeffrey T Borenstein,Ashley L Gard
Journal
Cells
Published Date
2023/11/16
OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers
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 annihilation. Testing has included larger molecules than in the past, and parameters are reported for the first time for some less common groups including alkynes, allenes, dienes, and acetals. The average errors in comparison with experimental data for the computed properties of the pure liquids were improved with the modified force field (OPLS/2020). For liquid densities and heats of vaporization, the average unsigned …
Authors
William L Jorgensen,Mohammad M Ghahremanpour,Anastasia Saar,Julian Tirado-Rives
Journal
The Journal of Physical Chemistry B
Published Date
2023/12/21
MIF modulators
The invention provides novel heterocyclic compounds, pharmaceutical compositions and methods of treatment that modulate levels of MIF expression and treat disorders associated with high or low levels of MIF expression.
Published Date
2023/2/21
Professor FAQs
What is William L. Jorgensen's h-index at Yale University?
The h-index of William L. Jorgensen has been 59 since 2020 and 133 in total.
What are William L. Jorgensen's top articles?
The articles with the titles of
Enthalpies and entropies of hydration from Monte Carlo simulations
Proof-of-concept studies with a computationally designed Mpro inhibitor as a synergistic combination regimen alternative to Paxlovid
Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase
Ensemble Geometric Deep Learning of Aqueous Solubility
Pyrazole-Containing Macrophage Migration Inhibitory Factor Inhibitors
A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening
OPLS/2020 Force Field for Unsaturated Hydrocarbons, Alcohols, and Ethers
MIF modulators
...
are the top articles of William L. Jorgensen at Yale University.
What are William L. Jorgensen's research interests?
The research interests of William L. Jorgensen are: Chemistry, Biochemistry
What is William L. Jorgensen's total number of citations?
William L. Jorgensen has 139,091 citations in total.
What are the co-authors of William L. Jorgensen?
The co-authors of William L. Jorgensen are Michael L Klein, Julian Tirado-Rives, James M. Briggs, Heather A. Carlson, Jeffry Madura.