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An essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1) is integration of the double-stranded retroviral DNA into the genome of the host cell. HIV-1 integrase, the enzyme that inserts the vital DNA into the host chromosome, is an attractive and rational target for anti-AIDS drug design because it is essential for HIV replication(More)
BACKGROUND Transcription of HIV-1 genes is activated by HIV-1 Tat protein, which induces phosphorylation of RNA polymerase II (RNAPII) C-terminal domain (CTD) by CDK9/cyclin T1. Earlier we showed that CDK2/cyclin E phosphorylates HIV-1 Tat in vitro. We also showed that CDK2 induces HIV-1 transcription in vitro and that inhibition of CDK2 expression by RNA(More)
BACKGROUND Breast cancer patients are at increased risk of osteoporosis. Contributing factors include age and/or chemotherapy. The selective estrogen modulator, raloxifene (RAL), effective in the prevention of breast cancer and approved for the treatment and prevention of osteoporosis, may prove beneficial in current breast cancer treatment modules. The(More)
Residue interaction networks and loop motions are important for catalysis in dihydrofolate reductase (DHFR). Here, we investigate the effects of ligand binding and chain connectivity on network communication in DHFR. We carry out systematic network analysis and molecular dynamics simulations of the native DHFR and 19 of its circularly permuted variants by(More)
The three-dimensional structure of the human dihydrofolate reductase (DHFR), methotrexate tetrazole, and NADPH ternary complex was used to model the corresponding ternary complexes with methotrexate tetrazole replaced by methotrexate, methotrexate-polyglutamate with three glutamyl residues, and 5,10-deazaaminopterin, respectively. Each complex was solvated(More)
Protein domains are structural and fundamental functional units of proteins. The information of protein domain boundaries is helpful in understanding the evolution, structures and functions of proteins, and also plays an important role in protein classification. In this paper, we propose a support vector regression-based method to address the problem of(More)
Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems(More)
BACKGROUND Pemetrexed (Alimta) is a new-generation multitargeted antifolate that inhibits several key enzymes in the de novo pathways of pyrimidine and purine biosynthesis, including thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). Alimta has demonstrated antitumor activity in a broad array(More)
The emergence of drug-resistant HIV-1 strains presents a challenge for the design of new drugs. Targeting host cell factors involved in the regulation of HIV-1 replication might be one way to overcome the resistance of HIV-1 to anti-viral agents. Our recent studies identified protein phosphatase-1 (PP1) as an important regulator of HIV-1 transcription.(More)