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Literature DB >> 17131993

FEP-guided selection of bicyclic heterocycles in lead optimization for non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Joseph T Kim¹, Andrew D Hamilton, Christopher M Bailey, Robert A Domaoal, Robert A Domoal, Ligong Wang, Karen S Anderson, William L Jorgensen.

Abstract

Monte Carlo simulations using free energy perturbation theory have been used to guide the selection of bicyclic heterocycles in the lead optimization of non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Good correlation is found between predicted and observed activities. Six compounds are reported with EC50 values below 20 nM for protection of human MT-2 cells against the cytopathogenicity of HIV-1. Striking variation in activity is found and analyzed for an isomeric pyrrolopyrimidine and pyrrolopyrazine pair.

Entities: Chemical Species

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Year: 2006 PMID： 17131993 DOI： 10.1021/ja066472g

Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419

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Cited

28 in total

Review 1. Prediction of protein-ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations.

Authors: Julien Michel; Jonathan W Essex
Journal: J Comput Aided Mol Des Date: 2010-05-28 Impact factor: 3.686

Review 2. Identification of HIV inhibitors guided by free energy perturbation calculations.

Authors: Orlando Acevedo; Zandrea Ambrose; Patrick T Flaherty; Hadega Aamer; Prashi Jain; Somisetti V Sambasivarao
Journal: Curr Pharm Des Date: 2012 Impact factor: 3.116

3. From docking false-positive to active anti-HIV agent.

Authors: Gabriela Barreiro; Joseph T Kim; Cristiano R W Guimarães; Christopher M Bailey; Robert A Domaoal; Ligong Wang; Karen S Anderson; William L Jorgensen
Journal: J Med Chem Date: 2007-10-06 Impact factor: 7.446

4. Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring.

Authors: Gabriela Barreiro; Cristiano R W Guimarães; Ivan Tubert-Brohman; Theresa M Lyons; Julian Tirado-Rives; William L Jorgensen
Journal: J Chem Inf Model Date: 2007-10-20 Impact factor: 4.956

10. Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures.

Authors: Sara E Nichols; Robert A Domaoal; Vinay V Thakur; Julian Tirado-Rives; Karen S Anderson; William L Jorgensen
Journal: J Chem Inf Model Date: 2009-05 Impact factor: 4.956

FEP-guided selection of bicyclic heterocycles in lead optimization for non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Review 1. Prediction of protein-ligand binding affinity by free energy simulations: assumptions, pitfalls and expectations.

Review 2. Identification of HIV inhibitors guided by free energy perturbation calculations.

3. From docking false-positive to active anti-HIV agent.

4. Search for non-nucleoside inhibitors of HIV-1 reverse transcriptase using chemical similarity, molecular docking, and MM-GB/SA scoring.

5. Computer-aided discovery of anti-HIV agents.

6. Energetics of displacing water molecules from protein binding sites: consequences for ligand optimization.

7. Novel naphthalene-based inhibitors of Trypanosoma brucei RNA editing ligase 1.

8. Optimization of azoles as anti-human immunodeficiency virus agents guided by free-energy calculations.

9. Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site.

10. Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures.