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The highly pathogenic H5N1 influenza virus, which is rapidly mutating and becoming increasingly drug-resistant, was investigated by means of structure-activity relationship between NA (neuraminidase) and three inhibitors, i.e., DANA (2,3-didehydro-2-deoxy-N-acetylneuraminic acid), zanamivir, and oseltamivir. A homology model of the H5N1-NA from the highly(More)
The M2 proton channel is one of indispensable components for the influenza A virus that plays a vital role in its life cycle and hence is an important target for drug design against the virus. In view of this, the three-dimensional structure of the H1N1-M2 channel was developed based on the primary sequence taken from a patient recently infected by the H1N1(More)
The human cytochrome P450 1A2 is an important drug metabolizing and procarcinogen activating enzyme. An experimental study found that a peripheral mutation, F186L, at ∼26 Å away from the enzyme's active site, caused a significant reduction in the enzymatic activity of 1A2 deethylation reactions. In this paper, we explored the effects of this mutation by(More)
In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed(More)
Cytochrome P450 2C19 (CYP2C19) is a member of the cytochrome P-450 enzyme superfamily and plays an important role in the metabolism of drugs. In order to gain insights for developing personalized drugs, the 3D (dimensional) structure of CYP2C19 has been developed based on the crystal structure of CYP2C9 (PDB code 1R90), and its structure-activity(More)
Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of many important drugs, including diclofenac. CYP2C9*3 and CYP2C9*13 are the principal variant alleles found in the Chinese population. CYP2C9*3 has been reported to reduce the metabolism of diclofenac and alter the extent of drug-drug interactions (DDIs). The effects of(More)
High throughput virtual screening is acknowledged as the initial means for identifying hit compounds that will be eventually transformed to leads or drug candidates. To improve quality of screening, it is essential to have powerful methods for the analysis of the compound databases. For this purpose, we have developed a novel and practical scoring function(More)
Pharmacophore modeling can provide valuable insight into ligand-receptor interactions. It can also be used in 3D (dimensional) database searching for potentially finding biologically active compounds and providing new research ideas and directions for drug-discovery projects. To stimulate the structure-based drug design against SARS (severe acute(More)
Protein tyrosine phosphatases 1B (PTP1B) is a major negative regulator of both insulin and leptin signaling pathways. In view of this, it becomes an important target for drug development against cancers, diabetes and obesity. The aim of the current study is to use the long time-scale molecular dynamics (MD) simulations to investigate the structural and(More)
Theoretical and molecular modeling studies have been conducted for understanding the details of how 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21) and its metabolism derivatives bind with the receptor of alpha7 nicotinic acetylcholine dimer. Good accordance with experimental results has been achieved. It was found that the van der Waals(More)