Exploring the conformational space of cyclic peptides by a stochastic search method
Exploring the conformational space of cyclic peptides by a stochastic search method
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DOI：
10.1016/j.jmgm.2003.12.012
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发表时间：
2004-05-01
影响因子：
2.9
通讯作者：
Goldblum, A
中科院分区：
文献类型：
--
作者：
Rayan, A;Senderowitz, H;Goldblum, A
为了探测环状肽的构象，采用了随机搜索算法。搜寻工作分两个阶段进行。在第一阶段，随机生成构象，并通过环闭合能力的惩罚函数进行评估，随后通过随机选择其允许的构象之一将每个氨基酸逐步构建到肽中。每个氨基酸的主二面角的允许构象范围已从不同蛋白质的数据库中提取出来。二面角的值，不有利于评分的环关闭保留或丢弃的统计检验。值被丢弃，直到一个点，所有剩余的角度组合被构造、评分、排序和聚类。在第二阶段，添加侧链，并使用Sybyl 6.8的“Kollman力场”，以“联合原子”的方式对不同构象集进行快速优化。与在适当规模的问题中进行完全穷举搜索相比，这种迭代随机消除算法可以找到全局最小和大多数最佳结果。在较大的问题中，我们将结果与实验结构进行比较。4 ~ 15个氨基酸大小的环状肽晶体结构的最佳结果的均方根偏差（RMSD）大多在1.0 ~ 8 μ m以下，较大的环状肽在2.0 μ m以下。(C) 2004爱思唯尔公司版权所有。
A stochastic search algorithm is applied in order to probe the conformations of cyclic peptides. The search is conducted in two stages. In the first stage, random conformations are generated and evaluated by a penalty function for ring closure ability, following a stepwise construction of each amino acid into the peptide by a random choice of one of its allowed conformations. The allowed conformational ranges of backbone dihedral angles for each amino acid have been extracted from a Data Bank of diverse proteins. Values of dihedral angles that do not contribute favorably to the scoring of ring closure are retained or discarded by a statistical test. Values are discarded up to a point from which all remaining combinations of angles are constructed, scored, sorted, and clustered. In the second stage, side chains have been added and fast optimization was applied to the set of diverse conformations in a "united atoms" approach, with the "Kollman forcefield" of Sybyl 6.8. This iterative stochastic elimination algorithm finds the global minimum and most of the best results, when compared to a full exhaustive search in appropriately sized problems. In larger problems, we compare the results to experimental structures. The root mean square deviation (RMSD) of our best results compared to crystal structures of cyclic peptides with sizes from 4 to 15 amino acids are mostly below 1.0 Angstrom up to 8 mers and under 2.0 Angstrom for larger cyclic peptides. (C) 2004 Elsevier Inc. All rights reserved.