Binding pathway of retinal to bacterio-opsin: A prediction by molecular dynamics simulations
Binding pathway of retinal to bacterio-opsin: A prediction by molecular dynamics simulations
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DOI：
10.1016/s0006-3495(97)78326-7
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发表时间：
1997-12-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Isralewitz, B;Izrailev, S;Schulten, K
从脱辅基蛋白和视网膜形成细菌视紫红质（bR）的实验研究，但实际的途径，包括进入点，是知之甚少。分子动力学模拟提供了一个令人惊讶的清晰预测。在蛋白质的跨膜部分中bR螺旋E和F之间的窗口可以被鉴定为视网膜的进入点。通过在0.2ns的时间段内对retinal施加一系列200-1000 pN范围内的外力来进行的操纵分子动力学允许一旦与Lys（216）的席夫碱键被切割，就从bR中提取该发色团。提取继续进行，直到视网膜尾形成具有Ala（144）、Met（145）和Ser（183）侧基的氢键网络，所述侧基排列出/入窗口。操作诱导的失真与拟合均方根偏差的坐标（忽略视网膜，水，和氢原子）小于1.9埃的时候，视网膜羰基到达蛋白质表面。提取视网膜所需的力是由于摩擦力，并不表明存在显著的潜在障碍。因此，模拟表明了一种结合视黄醇的途径。水分子被发现在结合过程中起着至关重要的作用。
Formation of bacteriorhodopsin (bR) from apoprotein and retinal has been studied experimentally, but the actual pathway, including the point of entry, is little understood. Molecular dynamics simulations provide a surprisingly clear prediction. A window between bR helices E and F in the transmembrane part of the protein can be identified as an entry point for retinal. Steered molecular dynamics, performed by applying a series of external forces in the range of 200-1000 pN over a period bf 0.2 ns to retinal, allows one to extract this chromophore from bR once the Schiff base bond to Lys(216) i, cleaved. Extraction proceeds until the retinal tail forms a hydrogen bond network with Ala(144), Met(145), and Ser(183) Side groups lining the exit/entry window. The manipulation induces a distortion with a fitted root mean square deviation of coordinates (ignoring retinal, water, and hydrogen atoms) of less than 1.9 Angstrom by the time the retinal carbonyl reaches the protein surface. The forces needed to extract retinal are due to friction and do not indicate significant potential barriers. The simulations therefore suggest a pathway for the binding of retinal. Water molecules are found to play a crucial role in the binding process.