Enzyme Selectivity of HIV Reverse Transcriptase: Conformations, Ligands, and Free Energy Partition
نویسندگان
چکیده
منابع مشابه
Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase
We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 i...
متن کاملHIV Nucleoside Reverse Transcriptase Inhibitors
Currently, 16 antiretroviral drugs are approved for treatment of HIV infection. However, even the best currently available regimens pose challenges with regard to adherence, toxicity, antiviral activity, and resistance. New drug development thus confronts the need for improved convenience and tolerability, reduced toxicity, and improved activity against both wild-type and drug-resistant viruses...
متن کاملNucleoside reverse transcriptase inhibitors and HIV mutagenesis.
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متن کامل4'-Acylated thymidine 5'-triphosphates: a tool to increase selectivity towards HIV-1 reverse transcriptase.
4'-Acylated thymidines represent a new class of DNA chain terminators, since they have been shown to act as post-incorporation chain-terminating nucleotides despite the presence of a free 3'-hydroxyl group. Here, we describe the action of the 4'-acetyl- (MeTTP) and 4'-propanoylthymidine 5'-triphosphate (EtTTP) on HIV-1 reverse transcriptase in RNA- and DNA-dependent DNA synthesis and on DNA syn...
متن کاملCollective motions in HIV-1 reverse transcriptase: examination of flexibility and enzyme function.
In order to study the inferences of structure for mechanism, the collective motions of the retroviral reverse transcriptase HIV-1 RT (RT) are examined using the Gaussian network model (GNM) of proteins. This model is particularly suitable for elucidating the global dynamic characteristics of large proteins such as the presently investigated heterodimeric RT comprising a total of 982 residues. L...
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ژورنال
عنوان ژورنال: The Journal of Physical Chemistry B
سال: 2015
ISSN: 1520-6106,1520-5207
DOI: 10.1021/acs.jpcb.5b05467