期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 120, 期 2, 页码 2271-2288出版社
WILEY
DOI: 10.1002/jcb.27553
关键词
Chlamydia trachomatis (Ct); density functional theory (DFT); docking; L ,L-diaminopimelate; aminotransferase; lysine biosynthesis; molecular dynamics (MD) simulation
资金
- Sciene Engineering and Research Board (SERB) [YSS/2014/000282]
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 (341519 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据