FtsZ靶向多肽抑制剂的分子对接、分子动力学分析及抗菌活性评价

Molecular docking,and molecular dynamic and antibacterial analyses of polypeptide inhibitors targeting FtsZ protein

为了得到靶向FtsZ的潜在肽类抑制剂和对其作用机制进行探究,采用分子对接方法筛选靶向金黄色葡萄球菌FtsZ蛋白的肽类化合物配体,利用分子动力学方法分析筛选到的配体与FtsZ蛋白结合状态的动态变化,计算配体重原子位置均方根偏差(RMSD)和相互作用能(Interaction energy)。在分子动力学分析基础上,分析以上短肽配体的抗菌活性,测定其对GTP酶活性的影响。结果表明,TE101、PE101、PE102、PE103和PE104五个多肽对于金黄色葡萄球菌的生长有抑制作用,且该作用与FtsZ蛋白GTPase活性无关。

The abuse of antibiotics has led to the emergence of drug-resistant bacteria,and new targets of antibiotics need to be developed urgently.FtsZ protein is a key protein in bacterial cell division,and inhibition of its dynamic process can lead to abnormal bacterial cell division and inhibition.In order to find bacterial inhibitors with new mechanisms of action,we conducted a virtual peptide screening by targeting the FtsZ protein of Staphylococcus aureus,and calculated the root mean square deviation(RMSD)and interaction energy of the screened peptides for evaluation.We investigated their binding stability,tested the antibacterial activity of the hit peptides,and measured their effects on GTPase to explore their mechanism of action.The screened five peptides,TE101,PE101,PE102,PE103 and PE104,were tested in combination with the results of molecular docking and molecular dynamics analysis.The results showed that these five peptides inhibited the growth of S.aureus,but did not act by affecting the GTPase of FtsZ protein.