三靶标抗抑郁活性分子虚拟筛选方法研究

项目名称： 三靶标抗抑郁活性分子虚拟筛选方法研究

项目编号： No.81202459

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 朱峰

作者单位： 重庆大学

项目金额： 23万元

中文摘要： 抑郁症作为全球最普遍的精神疾病，已对我国的国民健康造成了严重影响，并引起了广泛的关注。过去五十年间，对抗抑郁药物的研究已经取得了许多进展，但现有药物在见效时间、安全性和患者敏感性方面仍然有待提高。近年来，系统生物/药物学已经成为了研究热点。研究表明，三靶抗抑郁药物可有效抑制抑郁症复杂的网络发病机理，因此对这类药物的研究正在快速升温。为了大规模、高通量地筛选新型三靶标活性分子来作为抗抑郁药物设计的候选分子，本研究提出从计算机辅助药物设计角度，建立一套可靠的虚拟筛选方法。相较已报道的虚拟筛选方法，这套方法将不仅可以有效控制高通量筛选的假阳性率，还能从所得的筛选结果中进一步筛查副作用风险较低的活性分子。因此，本研究所提出的方法，无论从方法学还是所解决的具体药物化学问题上来说，都将对抗抑郁药物研究和开发起到积极的推动作用。

中文关键词： 三靶点抗抑郁剂；抑郁症；药物设计；虚拟筛选；假阳性

英文摘要： Major depression is a severe mental disorder which can lead to substantial impairments in an individual's ability to take care of his or her everyday responsibilities or even suicide. In the past five decades, a lot of drugs have been developed for treating major depression. However, there is still room before faster, safer and more sensitive antidepressant being marketed. Recently, drug design at network/system level has become the hot spot, and triple target antidepressants have accumulated much attention because they are capable of suppressing major depression related signaling pathways. In this work, we aim at developing a set of virtual screening methods for discovering large-scale and high-throughput novel triple-target antidepressant hits. Compared to the conventional methods, our methods is expected to be able to discover ture antidepressants with low false hit rate and identify less hits of undesired effects. Therefore, the methods proposed in this reseach is expected to be able to actively facilite the development of next generation antidepressants.

英文关键词： triple target antidepressants；major depression；drug design；virtual screening；false positive