Hierarchical database screenings for HIV-1 reverse transcriptase using a pharmacophore model, rigid docking, solvation docking, and MM-PB/SA. | LitMetric
Encysive Pharmaceuticals Inc., 7000 Fannin, Houston, Texas 77030, USA.
Published: April 2005
AI Article Synopsis
Article 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.
Background: Macrophage polarization and efferocytosis have been implicated in CHD. However, the underlying mechanisms remain elusive. This study aimed to identify CHD-associated biomarkers using transcriptomic data.
Remote ischemic conditioning (RIC) has attracted considerable attention as a brain protection strategy, although its impact remains unclear. Hypothermia is the most effective strategy in experimental transient cerebral ischemia. Therefore, we compared the efficacy of RIC, hypothermia, and no treatment on cerebral ischemia.
Pulmonary hypertension (PH) is a progressive disease characterized by vascular reHypoxiaing, endothelial cell dysfunction, and inflammation. Liver Kinase B1 (LKB1, also known as STK11) is a central regulator of cell polarity and energy homeostasis. However, its specific role and mechanism of action in PH remain unclear.
Background: The effect of initial antiretroviral therapy (ART) class on cancer risk in people with HIV (PWH) remains unclear.
Setting: Cohort study of 36,322 PWH enrolled (1996-2014) in the North American AIDS Cohort Collaboration on Research and Design.
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Introduction: Modification of natural enzymes to introduce new properties and enhance existing ones is a central challenge in bioengineering. This study is focused on the development of Taq polymerase mutants that show enhanced reverse transcriptase (RTase) activity while retaining other desirable properties such as fidelity, 5'- 3' exonuclease activity, effective deoxyuracyl incorporation, and tolerance to locked nucleic acid (LNA)-containing substrates. Our objective was to use AI-driven rational design combined with multiparametric wet-lab analysis to identify and validate Taq polymerase mutants with an optimal combination of these properties.
