近期,，華南農(nóng)業(yè)大學(xué)信息學(xué)院青年教師常珊博士的課題組在國際著名學(xué)術(shù)期刊Soft Matter雜志發(fā)表了研究論文,。該論文報道了大腸桿菌巖藻糖(L-fucose)轉(zhuǎn)運蛋白(FucP)的構(gòu)象變化和轉(zhuǎn)運過程的計算方法研究。
膜蛋白在各種重要的生物學(xué)過程中起著關(guān)鍵的作用,，轉(zhuǎn)運蛋白是膜蛋白中重要的組成部分,，大多數(shù)代謝上重要的分子和無機(jī)離子都通過細(xì)胞膜上的轉(zhuǎn)運蛋白進(jìn)行輸運。實驗上通過結(jié)構(gòu)解析可以得到轉(zhuǎn)運蛋白瞬態(tài)的靜態(tài)結(jié)構(gòu),，但轉(zhuǎn)運過程往往伴隨著明顯的構(gòu)象變化,。傳統(tǒng)的方法是通過分子動力學(xué)來進(jìn)行平衡態(tài)的模擬,，由于體系巨大,，模擬的時間尺度一般在數(shù)十納秒左右，而膜轉(zhuǎn)運蛋白的實際轉(zhuǎn)運過程尺度往往達(dá)到上百微秒量級（1微秒=1000納秒）,。因此,，對膜蛋白的變構(gòu)轉(zhuǎn)運模擬仍然具有極大的挑戰(zhàn)性。
該項研究采用計算的方法模擬了同向共轉(zhuǎn)運蛋白FucP轉(zhuǎn)運變構(gòu)過程,。實驗僅解析了FucP的外開口結(jié)構(gòu),，為了實現(xiàn)全過程模擬，作者首先采用結(jié)構(gòu)模建的方法構(gòu)建了內(nèi)開口狀態(tài)的FucP,。通過采用疊代的粗?；W(wǎng)絡(luò)方法，計算模擬了膜蛋白FucP從外開口結(jié)構(gòu)向內(nèi)開口結(jié)構(gòu)變化的過程,。該項研究與之前分子動力學(xué)的平衡態(tài)分析結(jié)果一致,，同時展示了分子動力學(xué)模擬難以達(dá)到的整個轉(zhuǎn)運的構(gòu)象變化過程。這種粗?；挠嬎隳M方法可以為膜蛋白的轉(zhuǎn)運機(jī)制研究提供幫助,。
該研究工作得到國家自然科學(xué)基金委項目(11047183)、廣東高校優(yōu)秀青年創(chuàng)新人才培育項目(LYM10042)和華南農(nóng)業(yè)大學(xué)校長基金項目(5600-k09325)資助,。
生物谷推薦英文摘要：
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.
