Thermodynamics and kinetics of folding of two model peptides investigated by molecular dynamics simulations
Thermodynamics and kinetics of folding of two model peptides investigated by molecular dynamics simulations
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DOI：
10.1021/jp994157t
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发表时间：
2000-05-25
影响因子：
3.3
通讯作者：
Caflisch, A
中科院分区：
文献类型：
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作者：
Ferrara, P;Apostolakis, J;Caflisch, A
折叠的α-螺旋和β-发夹进行了研究，通过862分子动力学模拟与隐式溶剂化模型，允许采样共4亩。除了在非常高的温度下的α-螺旋之外，对于具有小于约50%的折叠状态接触形成的构象，平均有效能量相当平坦。对于这两种肽，接近折叠状态的有效能量有一个平稳的下降。自由能图显示螺旋-卷曲转变不是一级的，而β-发夹有一个或两个最小值，这取决于温度。在低温下（T < 1.1T（m）），折叠速率随着温度的升高而增加，正如活化能有限过程所预期的那样。在较高温度下，两种肽的速率降低，这与活化熵主导的过程一致。相比之下，展开速率显示出类似于Arrhenius的行为，即，它随温度单调增加。在300 K下，β-发夹肽的折叠速度比α-螺旋肽慢约30倍。α-螺旋存在多种折叠途径，而β-发夹主要在β-转角处起始折叠。
The folding of an alpha-helix and a beta-hairpin was studied by 862 molecular dynamics simulations with an implicit solvation model that allowed sampling of a total of 4 mu s. The average effective energy is rather flat for conformations having less than about 50% of the folded state contacts formed, except for the alpha-helix at very high temperatures. For both peptides there is a smooth decrease of the effective energy close to the folded state. The free energy landscape shows that the helix-coil transition is not first order, while the beta-hairpin has one or two minima, depending on the temperature. At low temperature (T < 1.1T(m)) there is an increase in the folding rate with increasing temperature as expected from an activation energy limited process. At higher temperatures the rate decreases for both peptides which is consistent with an activation entropy dominated process. The unfolding rate, by contrast, shows an Arrhenius-like behavior, i.e., it increases monotonously with temperature. The beta-hairpin peptide folds about 30 times slower than the alpha-helix peptide at 300 K. Multiple folding pathways are present for the alpha-helix, whereas the beta-hairpin initiates folding mainly at the beta-turn.