TetraBASE: A Side Chain-Independent Statistical Energy for Designing Realistically Packed Protein Backbones
TetraBASE: A Side Chain-Independent Statistical Energy for Designing Realistically Packed Protein Backbones
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TetraBASE：一种独立于侧链的统计能量，用于设计真实包装的蛋白质主链
DOI：
10.1021/acs.jcim.7b00677
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发表时间：
2018-02
期刊：
影响因子：
--
通讯作者：
Haiyan Liu
中科院分区：
文献类型：
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作者：
Huanyu Chu;Haiyan Liu
构建具有高度可设计性的主链结构是计算蛋白质设计的一个主要方面。我们在这里报告了一个侧链独立的统计能量，旨在通过多肽骨架的空间包装的现实建模。为了减轻显式氨基酸侧链的缺乏，该模型将骨干间位点的包装视为依赖于肽的局部构象。此外，根据c α-碳原子周围不同化学基团的不对称四面体组织，引入了新的适合统计分析的变量（一个用于相对取向，另一个用于距离）来表示位点间几何形状。利用基于四面体的主链统计能量（tetraBASE）模型，从人工初始构型出发，利用Monte Caro模拟退火对指定类型的二级结构元（sse）的三级组织进行了优化。tetraBASE最小能量结构可以再现天然蛋白中常见的SSE堆积，原子均方根偏差为1-2 Å。该模型还通过检查本地SSE安排在tetraBASE下的稳定性进行了测试。结果表明，在不明确侧链类型的情况下，利用tetraBASE模型可以有效地表示骨架间的填充。
To construct backbone structures of high designability is a primary aspect of computational protein design. We report here a side chain-independent statistical energy that aims at realistic modeling of through-space packing of polypeptide backbones. To mitigate the lack of explicit amino acid side chains, the model treats the interbackbone site packing as being dependent on peptide local conformation. In addition, new variables suitable for statistical analysis, one for relative orientation and another for distance, have been introduced to represent the intersite geometry based on the asymmetrical tetrahedron organization of distinct chemical groups surrounding the Cα-carbon atoms. The resulting tetrahedron-based backbone statistical energy (tetraBASE) model has been used to optimize the tertiary organizations of secondary structure elements (SSEs) of designated types with Monte Caro simulated annealing, starting from artificial initial configurations. The tetraBASE minimum energy structures can reproduce SSE packing frequently observed in native proteins with atomic root-mean-square deviations of 1-2 Å. The model has also been tested by examining the stability of native SSE arrangements under tetraBASE. The results suggest that tetraBASE model can be used to effectively represent interbackbone packing when designing backbone structures without explicitly knowing side chain types.