Energy functions in de novo protein design: current challenges and future prospects.
Energy functions in de novo protein design: current challenges and future prospects.
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DOI：
10.1146/annurev-biophys-083012-130315
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发表时间：
2013
影响因子：
12.4
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Li Z;Yang Y;Zhan J;Dai L;Zhou Y
在过去的十年中，一个共同的努力，成功地捕捉特定的三级包装的相互作用产生了特定的三维结构的许多从头设计的蛋白质，通过核磁共振和/或X射线晶体学技术验证。然而，计算设计的成功率仍然很低。在这篇综述中，我们提供了一个实验验证的概述，从头设计的蛋白质和比较四个可用的程序，RosettaDesign，EGAD，梁Grishin和RosettaDesign-SR，通过评估设计的序列计算。计算评估包括天然序列的恢复，疏水补丁和总溶剂可及表面积的大小的计算，以及结构特性，如内在无序，二级结构和三维结构的预测。这种计算评估，加上最近的社区范围内的实验，在评估接口设计的评分功能，表明下一代蛋白质设计的评分功能将来自互补相互作用条款的正确平衡。当更多的负面实验数据成为训练集的一部分时，可以找到这种平衡。
In the past decade, a concerted effort to successfully capture specific tertiary packing interactions produced specific three-dimensional structures for many de novo designed proteins that are validated by nuclear magnetic resonance and/or X-ray crystallographic techniques. However, the success rate of computational design remains low. In this review, we provide an overview of experimentally validated, de novo designed proteins and compare four available programs, RosettaDesign, EGAD, Liang-Grishin, and RosettaDesign-SR, by assessing designed sequences computationally. Computational assessment includes the recovery of native sequences, the calculation of sizes of hydrophobic patches and total solvent-accessible surface area, and the prediction of structural properties such as intrinsic disorder, secondary structures, and three-dimensional structures. This computational assessment, together with a recent community-wide experiment in assessing scoring functions for interface design, suggests that the next-generation protein-design scoring function will come from the right balance of complementary interaction terms. Such balance may be found when more negative experimental data become available as part of a training set.
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