摘要
利用PharmMapper的反向药效团匹配方法对SAHA(伏立诺他)的潜在靶标进行筛选,虚拟筛选得到的HDLP,HDAC8等9个靶标已被实验研究证实。靶标所涉及的疾病与实验报道的SAHA的药理学活性一致,如抗癌、抗炎、抗肿瘤等作用。另外,预测出与老年痴呆、糖尿病、风湿性关节炎等疾病相关的SAHA的潜在靶标,进而利用分子对接技术对SAHA与潜在靶标的作用模式进行了研究。SAHA与潜在靶标的对接结果表明,它们在形状、电负性和疏水性方面匹配良好,能有效抑制靶标的活性。本实验研究表明,反药效团匹配和分子对接方法可作为预测药物潜在靶标的有效手段,为SAHA新的适用症的进一步研究提供理论指导。
In this research, the reverse mapping method PharmMapper was used to identify the potential targets of SAHA（Vorinostat）. Nine of the potential targets have been verified experimentally as the known targets inhibited by SAHA, such as HDLP, HDAC8 and so on. The relative deseases of potential targets matched the experiments reports of the pharmacologial activity of SAHA, including anticancer, antitumor and anti-inflammatory functions. Furthermore, some potential targets related to diseases including Alzheimer＇s disease, diabetes mellitus and rheumatoid arthritis were put forward. Molecule docking study was used to explore the binding mode between the protein candidates and SAHA. The docking results indicated that they were matched well in terms of structure, electronegativity and hydrophobicity. SAHA showed effective inhibitory activity for the potential targets. It shows that PharmMapper and molecule docking can be used as effective methods for potential targets prediction of drugs. The results can provide theoretical guidance for further study of new indications of SAHA.
出处
《计算机与应用化学》
CAS
CSCD
北大核心
2013年第1期97-101,共5页
Computers and Applied Chemistry
基金
北京市属高等学校人才强教深化计划中青年骨干人才项目(PHR20100718)
