Young W S, Brooks C L
Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
J Mol Biol. 1996 Jun 14;259(3):560-72. doi: 10.1006/jmbi.1996.0339.
Molecular dynamics simulations with umbrella sampling are used to perform free energy simulations of C-terminal and N-terminal helix propagation in small helices of Ace-(Ala)n-NMe, with n= (4,5,10,15), in water. From the resulting free energy surfaces, computed as a function of the terminal psi dihedral angle, the roles of length and end effects in helix propagation are explored. An energetic analysis of the helices, both formed and partially formed, is used to develop a molecular rationalization for the observed trends in helix stability. We find that the microscopic helix propagation parameters vary significantly depending on the end and length of the helix in which the terminal hydrogen bond is forming. A model which considers propagation of the helices from either end as statistically independent yields Zimm-Bragg s parameters in the range of 0.5 to 1.5, depending on helical length. Analysis of the mechanism of helix propagation suggests that 3(10)-helix plays a role in helix formation but its population should be low in the helical state of these model peptides.
使用带有伞形采样的分子动力学模拟对Ace-(Ala)n-NMe（n = 4、5、10、15）的小螺旋中C端和N端螺旋延伸进行自由能模拟，模拟环境为水。根据作为末端ψ二面角函数计算得到的自由能面，探究螺旋延伸中长度和末端效应的作用。对已形成和部分形成的螺旋进行能量分析，以对观察到的螺旋稳定性趋势进行分子层面的合理化解释。我们发现，微观螺旋延伸参数根据形成末端氢键的螺旋的末端和长度而有显著变化。一个将螺旋从任一端延伸视为统计独立的模型得出的齐姆-布拉格s参数在0.5到1.5范围内，具体取决于螺旋长度。对螺旋延伸机制的分析表明，3(10)螺旋在螺旋形成中起作用，但在这些模型肽的螺旋状态下其数量应该较低。
