Purisima E O, Scheraga H A
Baker Laboratory of Chemistry, Cornell University, Ithaca, NY 14853-1301.
J Mol Biol. 1987 Aug 5;196(3):697-709. doi: 10.1016/0022-2836(87)90041-6.
An algorithm for locating the region in conformational space containing the global energy minimum of a polypeptide is described. Distances are used as the primary variables in the minimization of an objective function that incorporates both energetic and distance-geometric terms. The latter are obtained from geometry and energy functions, rather than nuclear magnetic resonance experiments, although the algorithm can incorporate distances from nuclear magnetic resonance data if desired. The polypeptide is generated originally in a space of high dimensionality. This has two important consequences. First, all interatomic distances are initially at their energetically most favorable values; i.e. the polypeptide is initially at a global minimum-energy conformation, albeit a high-dimensional one. Second, the relaxation of dimensionality constraints in the early stages of the minimization removes many potential energy barriers that exist in three dimensions, thereby allowing a means of escaping from three-dimensional local minima. These features are used in an algorithm that produces short trajectories of three-dimensional minimum-energy conformations. A conformation in the trajectory is generated by allowing the previous conformation in the trajectory to evolve in a high-dimensional space before returning to three dimensions. The resulting three-dimensional structure is taken to be the next conformation in the trajectory, and the process is iterated. This sequence of conformations results in a limited but efficient sampling of conformational space. Results for test calculations on Met-enkephalin, a pentapeptide with the amino acid sequence H-Tyr-Gly-Gly-Phe-Met-OH, are presented. A tight cluster of conformations (in three-dimensional space) is found with ECEPP energies (Empirical Conformational Energy Program for Peptides) lower than any previously reported. This cluster of conformations defines a region in conformational space in which the global-minimum-energy conformation of enkephalin appears to lie.
本文描述了一种用于定位多肽构象空间中包含全局能量最小值区域的算法。在包含能量和距离几何项的目标函数最小化过程中，距离被用作主要变量。后者是从几何和能量函数中获得的，而不是通过核磁共振实验，不过如果需要，该算法也可以纳入来自核磁共振数据的距离。多肽最初在高维空间中生成。这有两个重要后果。首先，所有原子间距离最初都处于其能量上最有利的值；即多肽最初处于全局最小能量构象，尽管是高维的。其次，在最小化早期阶段放松维度约束消除了三维空间中存在的许多潜在能量障碍，从而提供了一种逃离三维局部最小值的方法。这些特征被用于一种算法中，该算法可生成三维最小能量构象的短轨迹。轨迹中的一个构象是通过让轨迹中前一个构象在返回三维之前在高维空间中演化而生成的。得到的三维结构被视为轨迹中的下一个构象，并重复该过程。这一系列构象导致对构象空间进行有限但有效的采样。给出了对甲硫氨酸脑啡肽（一种氨基酸序列为H-Tyr-Gly-Gly-Phe-Met-OH的五肽）的测试计算结果。发现了一组紧密的构象（在三维空间中），其ECEPP能量（肽的经验构象能量程序）低于此前报道的任何值。这组构象定义了构象空间中的一个区域，脑啡肽的全局最小能量构象似乎位于该区域。
