Protein folding simulation with solvent‐induced force field: Folding pathway ensemble of three‐helix‐bundle proteins
Protein folding simulation with solvent‐induced force field: Folding pathway ensemble of three‐helix‐bundle proteins
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DOI：
10.1002/1097-0134(20010101)42:1
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发表时间：
2001
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影响因子：
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通讯作者：
S. Takada
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作者：
S. Takada
我们提出了一个考虑溶剂效应的粗粒度蛋白质模型，并将其应用于模拟三螺旋束蛋白质的折叠。能量函数形式，从我们以前的工作中提炼出来（Takada等人，J Chem Phys 1999;110：11616-11629），试图密切模仿真实的物理化学相互作用。特别是，氢键依赖于局部介电常数，螺旋帽效应，侧链熵效应包括在内。利用该模型，我们模拟了白蛋白结合结构域1 prb 7 -53的GA模块的折叠，发现大多数轨迹在1 μs内到达天然拓扑结构。在模拟中，螺旋1和3大多在早期形成，伴随着非特异性崩溃，而第二螺旋本质上不太稳定，并且在后期阶段借助三级接触形成。我们计算过渡态系综的模拟，并将其与其他三螺旋束蛋白质进行比较。1 prb 7 -53的过渡态包括螺旋3的C末端与螺旋1和2之间的环区域的一些特定三级接触。这与葡萄球菌蛋白A片段B的早期形成区域相似，但不等同，但与从头设计的三螺旋束肽的折叠瞬时结构完全不同。蛋白质2001;42：85-98.© 2000 Wiley利斯公司
We propose a coarse‐grained model of proteins that take into account solvent effects and apply it for simulating folding of a three‐helix‐bundle protein. The energy functional form, refined from our previous work (Takada et al., J Chem Phys 1999;110:11616–11629), tries to closely imitate real physico‐chemical interactions. In particular, the hydrogen bond that depends on local dielectric constant, the helix capping effect, and side‐chain entropic effects are included. With use of the model, we simulate folding of the GA module of an albumin binding domain, 1prb7–53, finding most trajectories reach at the native topology within 1 μs. In the simulation, helices 1 and 3 are mostly formed earlier accompanied by non‐specific collapse, while second helix is intrinsically less stable and is formed with the help of tertiary contacts at later stage. We compute an analog of the transition state ensemble and compare it with those of other three‐helix‐bundle proteins. The transition state of 1prb7–53 includes a few specific tertiary contacts of C terminus of helix 3 with the loop region between helices 1 and 2. This resembles, but is not equivalent to, an early formed region of fragment B of staphylococcal protein A, but is quite different from the folding transient structures of a de novo designed three‐helix‐bundle peptide. Proteins 2001;42:85–98. © 2000 Wiley‐Liss, Inc.