School of Life Sciences, University of Science and Technology of China , 230027 Hefei, Anhui China.
Hefei National Laboratory for Physical Sciences at the Microscales , 230027 Hefei, Anhui China.
J Chem Inf Model. 2018 Feb 26;58(2):430-442. doi: 10.1021/acs.jcim.7b00677. Epub 2018 Feb 4.
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.
构建高设计性的骨架结构是计算蛋白质设计的一个主要方面。我们在这里报告一种侧链独立的统计能量，旨在对多肽骨架的贯穿空间堆积进行现实建模。为了减轻缺乏明确氨基酸侧链的问题，该模型将骨架间位点的堆积处理为依赖于肽的局部构象。此外，已经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，以基于围绕 Cα 碳原子的不同化学基团的不对称四面体组织来表示位点间的几何形状。所得到的基于四面体的骨架统计能量（tetraBASE）模型已被用于通过蒙特卡罗模拟退火从人工初始构象开始优化指定类型的二级结构元件（SSE）的三级组织。tetraBASE 最小能量结构可以再现原子均方根偏差为 1-2 Å 的天然蛋白质中经常观察到的 SSE 堆积。该模型还通过检查在 tetraBASE 下天然 SSE 排列的稳定性进行了测试。结果表明，当在不明确知道侧链类型的情况下设计骨架结构时，tetraBASE 模型可以有效地表示骨架间的堆积。
