Free energy surfaces of β-hairpin and α-helical peptides generated by replica exchange molecular dynamics with the AGBNP implicit solvent model
Free energy surfaces of β-hairpin and α-helical peptides generated by replica exchange molecular dynamics with the AGBNP implicit solvent model
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DOI：
10.1002/prot.20104
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发表时间：
2004-08-01
影响因子：
2.9
通讯作者：
Levy, RM
中科院分区：
文献类型：
--
作者：
Felts, AK;Harano, Y;Levy, RM
我们研究了两种肽的平均力的潜力，一种已知在溶液中采用β-发夹构象，另一种采用α-螺旋构象。这些肽分别是蛋白G的B1结构域的C-末端的残基41-56（GEWTYDDATKTFTVTE）和核糖核酸酶A的13残基C-肽（KETAAAKFERQHM）。广泛的规范系综采样已被使用的并行副本交换方法。在这项工作中采用的有效势由OPLS的全原子力场（OPLS-AA）和分析广义玻恩（AGB）隐式溶剂模型，包括一个新的非极性溶剂化自由能估计（NP）。一个额外的介电屏蔽参数已被纳入AGBNP模型。在β-发夹的情况下，非极性溶剂化自由能估计提供了必要的有效相互作用的疏水核心（W 43，Y 45，F52和V54）的崩溃，更常用的表面积依赖性非极性模型不提供。对于β-发夹和α-螺旋，增加的介电屏蔽降低了不正确形成的盐桥的稳定性，盐桥倾向于分别破坏发夹和螺旋的形成。我们用AGBNP模型得到的β-发夹和α-螺旋含量的分数与实验结果吻合得很好。如用OPLS-AA/ AGBNP有效势建模的来自蛋白G的β-发夹和来自核糖核酸酶A的α-螺旋C-肽的热力学稳定性反映了驱动压实的非极性有效势项与促进二级结构形成的极性和氢键键合项之间的平衡。(C)2004 Wiley-Liss，Inc.
We have studied the potential of mean force of two peptides, one known to adopt a beta-hairpin and the other an alpha-helical conformation in solution. These peptides are, respectively, residues 41-56 of the C-terminus (GEWTYDDATKTFTVTE) of the B1 domain of protein G and the 13 residue C-peptide (KETAAAKFERQHM) of ribonuclease A. Extensive canonical ensemble sampling has been performed using a parallel replica exchange method. The effective potential employed in this work consists of the OPLS all-atom force field (OPLS-AA) and an analytical generalized Born (AGB) implicit solvent model including a novel nonpolar solvation free energy estimator (NP). An additional dielectric screening parameter has been incorporated into the AGBNP model. In the case of the beta-hairpin, the nonpolar solvation free energy estimator provides the necessary effective interactions for the collapse of the hydrophobic core (W43, Y45, F52, and V54), which the more commonly used surface-area-dependent nonpolar model does not provide. For both the beta-hairpin and the a-helix, increased dielectric screening reduces the stability of incorrectly formed salt bridges, which tend to disrupt the formation of the hairpin and helix, respectively. The fraction of beta-hairpin and alpha-helix content we obtained using the AGBNP model agrees well with experimental results. The thermodynamic stability of the beta-hairpin from protein G and the alpha-helical C-peptide from ribonuclease A as modeled with the OPLS-AA/ AGBNP effective potential reflects the balance between the nonpolar effective potential terms, which drive compaction, and the polar and hydrogen bonding terms, which promote secondary structure formation. (C) 2004 Wiley-Liss, Inc.