Hierarchical database screenings for HIV-1 reverse transcriptase using a pharmacophore model, rigid docking, solvation docking, and MM-PB/SA
- PMID: 15801834
- DOI: 10.1021/jm049606e
Hierarchical database screenings for HIV-1 reverse transcriptase using a pharmacophore model, rigid docking, solvation docking, and MM-PB/SA
Abstract
In this work, an efficient strategy was presented to search drug leads for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) using hierarchical database screenings, which included a pharmacophore model, multiple-conformation rigid docking, solvation docking, and molecular mechanics-Poisson-Boltzmann/surface area (MM-PB/SA) sequentially. Encouraging results were achieved in searching a refined available chemical directory (ACD) database: the enrichment factor after the first three filters was estimated to be 25-fold; the hit rate for all the four filters was predicted to be 41% in a control test using 37 known HIV-1 non-nucleoside reverse transcriptase inhibitors; 10 out of 30 promising solvation-docking hits had MM-PB/SA binding free energies better than -6.8 kcal/mol and the best one, HIT15, had -17.0 kcal/mol. In conclusion, the hierarchical multiple-filter database searching strategy is an attractive strategy in drug lead exploration.
Similar articles
-
Docking of non-nucleoside inhibitors: neotripterifordin and its derivatives to HIV-1 reverse transcriptase.Proteins. 2002 Dec 1;49(4):529-42. doi: 10.1002/prot.10233. Proteins. 2002. PMID: 12402361
-
A pharmacophore docking algorithm and its application to the cross-docking of 18 HIV-NNRTI's in their binding pockets.Proteins. 2004 Feb 15;54(3):526-33. doi: 10.1002/prot.10599. Proteins. 2004. PMID: 14748000
-
Relative free energy of binding and binding mode calculations of HIV-1 RT inhibitors based on dock-MM-PB/GS.Proteins. 2004 Nov 15;57(3):493-503. doi: 10.1002/prot.20223. Proteins. 2004. PMID: 15382241
-
Pyridin-2(1H)-ones: a promising class of HIV-1 non-nucleoside reverse transcriptase inhibitors.ChemMedChem. 2007 Aug;2(8):1141-7. doi: 10.1002/cmdc.200700054. ChemMedChem. 2007. PMID: 17477343 Review. No abstract available.
-
Structural basis for drug resistance mechanisms for non-nucleoside inhibitors of HIV reverse transcriptase.Virus Res. 2008 Jun;134(1-2):157-70. doi: 10.1016/j.virusres.2007.12.018. Epub 2008 Mar 3. Virus Res. 2008. PMID: 18313784 Review.
Cited by
-
The Advances and Limitations of the Determination and Applications of Water Structure in Molecular Engineering.Int J Mol Sci. 2023 Jul 22;24(14):11784. doi: 10.3390/ijms241411784. Int J Mol Sci. 2023. PMID: 37511543 Free PMC article. Review.
-
Identification of highly effective inhibitors against SARS-CoV-2 main protease: From virtual screening to in vitro study.Front Pharmacol. 2022 Nov 18;13:1036208. doi: 10.3389/fphar.2022.1036208. eCollection 2022. Front Pharmacol. 2022. PMID: 36467060 Free PMC article.
-
Fast Identification of Possible Drug Treatment of Coronavirus Disease -19 (COVID-19) Through Computational Drug Repurposing Study.ChemRxiv [Preprint]. 2020 Feb 21. doi: 10.26434/chemrxiv.11875446. ChemRxiv. 2020. Update in: J Chem Inf Model. 2020 Jun 22;60(6):3277-3286. doi: 10.1021/acs.jcim.0c00179 PMID: 32510523 Free PMC article. Updated. Preprint.
-
Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study.J Chem Inf Model. 2020 Jun 22;60(6):3277-3286. doi: 10.1021/acs.jcim.0c00179. Epub 2020 May 4. J Chem Inf Model. 2020. PMID: 32315171 Free PMC article.
-
Structural Basis of TLR2/TLR1 Activation by the Synthetic Agonist Diprovocim.J Med Chem. 2019 Mar 28;62(6):2938-2949. doi: 10.1021/acs.jmedchem.8b01583. Epub 2019 Mar 13. J Med Chem. 2019. PMID: 30829478 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
