Pharmacophore-Based Screening and Identification of Molecular-Level Descriptors Applied to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
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Manuscript has been submitted and in review by the National High School Journal of Science, 2020
ABSTRACT
Retroviruses such as HIV use the reverse transcriptase (RT) enzyme to transcribe their viral RNA into DNA, which is subsequently incorporated into the human host cell genome and expressed to replicate the virus. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a class of antiretroviral drugs that have been used to treat human immunodeficiency virus (HIV) infections. In any small molecule bioactive compound, two important structural features that
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define the thermodynamics of ligand-receptor binding are the 3-dimensional orientation and positioning of hydrogen bond donor/acceptor sites and aromatic rings, which form hydrogen bonds and pi-stacking interactions, respectively with the target. Here, scripts to determine heteroatom and aromatic ring positions were written in the programming language Python, generating the Cartesian coordinates of these structural features in a 3-dimensional map. This allowed for the creation of a descriptor-driven platform that can identify and statistically analyze the structural correlation across a library of structurally diverse chemical entities that bind to a known biomolecular target, such as HIV-RT. Six FDAapproved NNRTIs and three non-FDA-approved NNRTIs were analyzed using PaDEL-Descriptor, a molecular characteristics quantification program, to determine and identify structural similarities among molecules that have displayed potent biological activity against HIV-RT. [Full Article Link]
