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Identification of potential drugs targeting L,L‐diaminopimelate aminotransferase of Chlamydia trachomatis : An integrative pharmacoinformatics approach
Author(s) -
Sadhasivam Anupriya,
Vetrivel Umashankar
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27553
Subject(s) - chlamydia trachomatis , prioritization , molecular mechanics , chemistry , computational biology , biology , molecular dynamics , virology , computational chemistry , management science , economics
Abstract Chlamydia trachomatis (C.t) is a gram‐negative obligate intracellular bacteria, which is a major causative of infectious blindness and sexually transmitted diseases. A surge in multidrug resistance among chlamydial species has posed a challenge to adopt alternative drug targeting strategies. Recently, in C.t, L,L‐diaminopimelate aminotransferase (CtDAP‐AT) is proven to be a potential drug target due its essential role in cell survival and host nonspecificity. Hence, in this study, a multilevel precision‐based virtual screening of CtDAP‐AT was performed to identify potential inhibitors, wherein, an integrative stringent scoring and filtration were performed by coupling, glide docking score, binding free energy, ADMET (absorption, distribution, metabolism, and excretion, toxicity) prediction, density functional theory (quantum mechanics), and molecular dynamics simulation (molecular mechanics). On cumulative analysis, NSC_5485 (1,3‐bis((7‐chloro‐4‐quinolinyl)amino)‐2‐propanol) was found to be the most potential lead, as it showed higher order significance in terms of binding affinity, bonded interactions, favorable ADMET, chemical reactivity, and greater stabilization during complex formation. This is the first report on prioritization of small molecules from National Cancer Institute (NCI) and Maybridge data sets (341 519 compounds) towards targeting CtDAP‐AT. Thus, the proposed compound shall aid in effective combating of a broad spectrum of C.t infections as it surpassed all the levels of prioritization.