Monte carlo folding of trans‐membrane helical peptides in an implicit generalized Born membrane
Monte carlo folding of trans‐membrane helical peptides in an implicit generalized Born membrane
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隐式广义 Born 膜中跨膜螺旋肽的蒙特卡罗折叠
DOI：
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
A. di Nola
中科院分区：
文献类型：
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作者：
J. Ulmschneider;M. Ulmschneider;A. di Nola
将协同骨架旋转的蒙特卡罗(MC)算法与最近发展的隐式膜模型相结合，模拟了甲型流感病毒M2蛋白和Sarcolipin的疏水跨膜结构域M2TM在原子分辨率下的折叠。隐式膜环境基于广义Born理论，并根据实验数据进行了校准。MC采样以前曾用于折叠几个小的多肽，并被证明是等价于分子动力学(MD)的。结合复制交换算法，发现M2TM可以为低温复制形成跨越螺旋构象的连续膜。Sarcolipin只是部分螺旋的，与实验中在脂质双层和洗涤剂胶束中的核磁共振结构一致。温度较高的复制品表现出螺旋度的迅速下降，这与预期的热力学行为一致。为了排除模拟中错误的螺旋偏差的可能性，通过采样已知螺旋度的合成富含丙氨酸的多肽来测试该模型。结果表明，M2TM和Sarcolipin的螺旋构象不存在过稳定现象，这表明隐式模型捕捉到了天然膜环境的基本成分。蛋白质2007。©2007 Wiley-Liss Inc.
An efficient Monte Carlo (MC) algorithm using concerted backbone rotations is combined with a recently developed implicit membrane model to simulate the folding of the hydrophobic transmembrane domain M2TM of the M2 protein from influenza A virus and Sarcolipin at atomic resolution. The implicit membrane environment is based on generalized Born theory and has been calibrated against experimental data. The MC sampling has previously been used to fold several small polypeptides and been shown to be equivalent to molecular dynamics (MD). In combination with a replica exchange algorithm, M2TM is found to form continuous membrane spanning helical conformations for low temperature replicas. Sarcolipin is only partially helical, in agreement with the experimental NMR structures in lipid bilayers and detergent micelles. Higher temperature replicas exhibit a rapidly decreasing helicity, in agreement with expected thermodynamic behavior. To exclude the possibility of an erroneous helical bias in the simulations, the model is tested by sampling a synthetic Alanine‐rich polypeptide of known helicity. The results demonstrate there is no overstabilization of helical conformations, indicating that the implicit model captures the essential components of the native membrane environment for M2TM and Sarcolipin. Proteins 2007. © 2007 Wiley‐Liss, Inc.
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