中文摘要：

鞘磷脂 synthase (SMS ) 从 ceramide 和 phosphatidylcholine 生产鞘磷脂和 diacylglycerol。它在房间起一个重要作用幸存和 apoptosis，发炎，和类脂化合物动态平衡，并且因此作为一篇小说在最近的年里被注意了潜在的药目标。在这研究，我们联合了相同建模，分子的停靠、分子的动力学模拟，和导出在有鞘磷脂的建筑群的人的鞘磷脂 synthase (hSMS1 ) 的三维的结构的正常模式分析。我们的模型在 hSMS1 的催化机制上提供合理解释。它能也关于 hSMS1 象一些另外的已知的试验性的结果一样向 phosphocholine 和鞘磷脂解释 hSMS1 的高选择。而且，我们也导出 D609 的一个复杂模型， hSMS1 的唯一的已知的小分子的禁止者到目前为止。我们的 hSMS1 模型可以用作 hSMS1 的更有效的小分子的禁止者的发现的一个合理结构的基础。

英文摘要：

Sphingomyelin synthase （SMS） produces sphingomyelin and diacylglycerol from ceramide and phosphatidyl- choline. It plays an important role in cell survival and apoptosis, inflammation, and lipid homeostasis, and therefore has been noticed in recent years as a novel potential drug target. In this study, we combined homology modeling, molecular docking, molecular dynamics simulation, and normal mode analysis to derive a three-dimensional struc- ture of human sphingomyelin synthase （hSMS 1） in complex with sphingomyelin. Our model provides a reasonable explanation on the catalytic mechanism of hSMS 1. It can also explain the high selectivity of hSMS 1 towards phos- phocholine and sphingomyelin as well as some other known experimental results about hSMS1. Moreover, we also derived a complex model of D609, the only known small-molecule inhibitor of hSMS 1 so far. Our hSMS 1 model may serve as a reasonable structural basis for the discovery of more effective small-molecule inhibitors of hSMS 1.