How to guarantee optimal stability for most representative structures in the protein data bank
How to guarantee optimal stability for most representative structures in the protein data bank
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DOI：
10.1002/prot.1075
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发表时间：
2001-08-01
期刊：
影响因子：
--
通讯作者：
Vendruscolo, M
中科院分区：
文献类型：
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作者：
Bastolla, U;Farwer, J;Vendruscolo, M
我们最近提出了一种优化方法来获得简化的蛋白质折叠模型的能量参数。该方法是基于最大化的热力学平均蛋白质的天然结构和玻尔兹曼系综的替代结构之间的重叠。这样的条件强制蛋白质模型，其基态与相应的天然状态最相似。我们在这里提出了一个广泛的测试的方法，一个简单的残留物-残留物接触能函数和替代结构产生的线程。优化的能量函数保证了PDB数据库中最具代表性的结构的高稳定性和良好相关的能量景观。天然结构的识别失败可以归因于忽略寡聚蛋白质中不同链之间的相互作用或与辅因子的相互作用，当考虑到这些时，只有很少的X射线结构未被识别。它们中的大多数是短的抑制剂或片段，并且一个是呈现严重不一致的结构。最后，我们讨论了使NMR结构更难识别的原因。(C)2001 Wiley-Liss，Inc.
We proposed recently an optimization method to derive energy parameters for simplified models of protein folding. The method is based on the maximization of the thermodynamic average of the overlap between protein native structures and a Boltzmann ensemble of alternative structures. Such a condition enforces protein models whose ground states are most similar to the corresponding native states. We present here an extensive testing of the method for a simple residue-residue contact energy function and for alternative structures generated by threading. The optimized energy function guarantees high stability and a well-correlated energy landscape to most representative structures in the PDB database. Failures in the recognition of the native structure can be attributed to the neglect of interactions between different chains in oligomeric proteins or with cofactors, When these are taken into account, only very few X-ray structures are not recognized. Most of them are short inhibitors or fragments and one is a structure that presents serious inconsistencies. Finally, we discuss the reasons that make NMR structures more difficult to recognize. (C) 2001 Wiley-Liss, Inc.