Simulation of the folding equilibrium of α-helical peptides:: A comparison of the generalized born approximation with explicit solvent
Simulation of the folding equilibrium of α-helical peptides:: A comparison of the generalized born approximation with explicit solvent
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DOI：
10.1073/pnas.2232868100
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发表时间：
2003-11-25
影响因子：
11.1
通讯作者：
García, AE
中科院分区：
文献类型：
--
作者：
Nymeyer, H;García, AE
我们比较模拟使用广义玻恩/表面积（GB/SA）隐式溶剂模型与模拟使用显式溶剂（可转移分子间势3点，TIP 3 P）测试GB/SA算法。我们使用复制交换分子动力学方法，通过两种不同的经典势和两种水模型，对两个α-螺旋肽A（21）和F-s的构象相空间进行了采样.我们发现，当使用GB/SA时：（i）预测A（21）在所有温度下都比F-s肽更螺旋;（ii）预测F-s肽的天然结构是螺旋束而不是单螺旋;（iii）与明确的溶剂模拟相比，未折叠状态下的持久长度和最可能的端到端距离太大。我们发现，在phipsi平面的平均力的潜力是显着不同的两种溶剂中，使两个模拟肽响应不同时，骨干扭转扰动。在这些模拟中获得的温度熔化曲线的Lifson-Roig模型的拟合发现，GB/SA模型具有非物理大的成核参数，而显式溶剂模型产生的值类似于实验。
We compare simulations using the generalized Born/surface area (GB/SA) implicit solvent model with simulations using explicit solvent (transferable intermolecular potential 3 point, TIP3P) to test the GB/SA algorithm. We use the replica exchange molecular dynamics method to sample the conformational phase space of two a-helical peptides, A(21) and the F-s, by using two different classical potentials and both water models. We find that when using GB/SA: (i) A(21) is predicted to be more helical than the F-s peptide at all temperatures; (ii) the native structure of the F-s peptide is predicted to be a helical bundle instead of a single helix; and (iii) the persistence length and most probable end-to-end distance are too large in the unfolded state when compared against the explicit solvent simulations. We find that the potential of mean force in the phipsi plane is markedly different in the two solvents, making the two simulated peptides respond differently when the backbone torsions are perturbed. A fit of the temperature melting curves obtained in these simulations to a Lifson-Roig model finds that the GB/SA model has an unphysically large nucleation parameter, whereas the explicit solvent model produces values similar to experiment.