近期，华南农业大学信息学院青年教师常珊博士的课题组在国际著名学术期刊Soft Matter杂志发表了研究论文。该论文报道了大肠杆菌岩藻糖(L-fucose)转运蛋白(FucP)的构象变化和转运过程的计算方法研究。
膜蛋白在各种重要的生物学过程中起着关键的作用，转运蛋白是膜蛋白中重要的组成部分，大多数代谢上重要的分子和无机离子都通过细胞膜上的转运蛋白进行输运。实验上通过结构解析可以得到转运蛋白瞬态的静态结构，但转运过程往往伴随着明显的构象变化。传统的方法是通过分子动力学来进行平衡态的模拟，由于体系巨大，模拟的时间尺度一般在数十纳秒左右，而膜转运蛋白的实际转运过程尺度往往达到上百微秒量级（1微秒=1000纳秒）。因此，对膜蛋白的变构转运模拟仍然具有极大的挑战性。
该项研究采用计算的方法模拟了同向共转运蛋白FucP转运变构过程。实验仅解析了FucP的外开口结构，为了实现全过程模拟，作者首先采用结构模建的方法构建了内开口状态的FucP。通过采用叠代的粗粒化网络方法，计算模拟了膜蛋白FucP从外开口结构向内开口结构变化的过程。该项研究与之前分子动力学的平衡态分析结果一致，同时展示了分子动力学模拟难以达到的整个转运的构象变化过程。这种粗粒化的计算模拟方法可以为膜蛋白的转运机制研究提供帮助。
该研究工作得到国家自然科学基金委项目(11047183)、广东高校优秀青年创新人才培育项目(LYM10042)和华南农业大学校长基金项目(5600-k09325)资助。
生物谷推荐英文摘要：
Soft Matter, 2011, 7 (10), 4661 - 4671, DOI: 10.1039/C0SM01543A
Allosteric and transport behavior analyses of a fucose transporter with network models
Shan Chang, Kang-shun Li, Jian-ping Hu, Xiong Jiao and Xu-hong Tian
The major facilitator superfamily (MFS) is an important and widespread family of secondary membrane transporters. Recently, an outward-open structure of MFS, the fucose/H+ symporter FucP was determined by X-ray crystallography. In this article, the outward-open form of FucP is analyzed by elastic network models. It is found that the periplasmic half region has remarkable fluctuation, and the closure of the periplasmic half is the most dominant conformational change for outward-open conformation of FucP. To ascertain the process of transport, an adaptive anisotropic network model is applied to explore the allosteric transitions of FucP. In particular, our simulation not only yields the intermediate states similar to that seen in the EmrD crystal structure, but also exhibits the whole transport process of FucP. On the basis of the coarse-grained analyses, we propose a new working model of how FucP mediates the symport of L-fucose and a proton. The allosteric and transport knowledge of FucP revealed in this work can provide some insights into the mechanism studies of MFS and other transport proteins.
