Department of Biotechnology, National Institute of Technology Raipur, Raipur, India.
Curr Drug Targets. 2018;19(13):1589-1598. doi: 10.2174/1389450119666171129164932.
Due to increase in antibiotic-resistance among pathogens, there is a need for potent and safe drugs. An alternative to antibiotics is lipopeptides which are produced as a secondary metabolite by many microorganisms. They exhibit broad-spectrum activities against pathogens along with anticancer properties. Among various lipopeptides produced by microorganisms, daptomycin, surfactin, and polymyxin have gained popularity as medicines but their mechanism of action is not described properly. In silico drug design of these lipopeptides becomes a challenge due to their complex structures. In order to initiate a physiological response, specific agonists (ligands) of their receptor (lipopeptide) must be identified.
The objective of this study was molecular docking of three lipopeptides, daptomycin, surfactin and polymyxin, with their ligands as a means of drug design.
Schrödinger software was used for molecular docking of lipopeptides with their corresponding ligands whereas the ligand search was done using RCSB. Once the ligands were identified, they were docked with their corresponding lipopeptide. Docking score and glide energy were used as the parameters to test docking.
All four of the identified ligands were found to dock with daptomycin, whereas for both surfactin and polymyxin one out of two ligands docked with the lipopeptides.
The knowledge of the docking sites and docking characteristics of the lipopeptide 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.
由于病原体对抗生素的耐药性不断增加，因此需要开发有效且安全的药物。抗生素的替代品是脂肽，它是许多微生物作为次级代谢产物产生的。它们对病原体具有广谱活性，同时具有抗癌特性。在微生物产生的各种脂肽中，达托霉素、表面活性剂和多粘菌素已作为药物广受欢迎，但它们的作用机制尚未得到充分描述。由于其复杂的结构，这些脂肽的计算机药物设计成为一项挑战。为了引发生理反应，必须确定其受体（脂肽）的特定激动剂（配体）。
本研究的目的是通过分子对接研究三种脂肽（达托霉素、表面活性剂和多粘菌素）与其配体，以此作为药物设计的一种方法。
使用 Schrödinger 软件对接脂肽与其相应的配体，而配体搜索则使用 RCSB 进行。一旦确定了配体，就将其与相应的脂肽对接。对接评分和 Glide 能量被用作测试对接的参数。
所有鉴定出的配体都与达托霉素对接，而对于表面活性剂和多粘菌素，两种配体中有一种与脂肽对接。
本文中提到的脂肽与配体对接的位点和对接特征的知识可以提供以下优势：高速、可靠、降低化学品和实验成本，以及避免使用动物模型筛选药物毒性所涉及的伦理问题。
