Eswari J Satya, Dhagat Swasti, Kaser Shubham, Tiwari Anoop
Department of Biotechnology, National Institute of Technology Raipur, Raipur-492010, India.
Department of Humanities and Social Sciences, National Institute of Technology Raipur, Raipur-492010, India.
Curr Drug Discov Technol. 2018;15(2):132-141. doi: 10.2174/1570163814666170816112536.
Lipopeptide synthetases play an important role in the production of lipopeptides. Lipopeptides are molecules made up of peptides and fatty acid moieties and have shown to have a broad range of antimicrobial activity. As infectious diseases have caused severe health problems mainly resulting from the development of antibiotic resistant strains of disease causing microorganisms there is a need of alternatives to antibiotics. The lipopeptide synthetase of the corresponding lipopeptides can be used as template to design these as drugs using computational techniques.
The objective of this study was homology modeling and molecular docking of two lipopeptide synthetases, bacillomycin D synthetase and iturin A synthetase, with their ligands as a means of drug design.
Schrödinger software was used for homology modeling and molecular docking.
After the identification of ligands, molecular docking of these ligands with the lipopeptide (bacillomycin and iturin) synthetases was performed. The docking was tested on the parameters of docking score and glide energy. 5 out of 21 ligands were found to dock with bacillomycin D synthetase whereas 8 out of 20 ligands docked with the iturin A synthetase.
The knowledge of the docking sites and docking characteristics of the lipopeptide synthetases mentioned in the paper with the ligands can provide advantages of high speed and reliability, reduced costs on chemicals and experiments and the ethical issues concerned with the use of animal models for screening of drug toxicity.
脂肽合成酶在脂肽的产生中起重要作用。脂肽是由肽和脂肪酸部分组成的分子，已显示具有广泛的抗菌活性。由于传染病主要因致病微生物的抗生素耐药菌株的出现而导致严重的健康问题，因此需要抗生素的替代品。相应脂肽的脂肽合成酶可以用作模板，利用计算技术将其设计为药物。
本研究的目的是对两种脂肽合成酶，即杆菌霉素D合成酶和伊枯草菌素A合成酶，与其配体进行同源建模和分子对接，作为药物设计的一种手段。
使用薛定谔软件进行同源建模和分子对接。
在鉴定出配体后，将这些配体与脂肽（杆菌霉素和伊枯草菌素）合成酶进行分子对接。对接在对接分数和滑行能量参数上进行了测试。发现21种配体中有5种与杆菌霉素D合成酶对接，而20种配体中有8种与伊枯草菌素A合成酶对接。
本文中提到的脂肽合成酶与配体的对接位点和对接特性的知识可以提供高速和可靠的优势，降低化学品和实验成本以及与使用动物模型筛选药物毒性相关的伦理问题。
