TOUCHSTONEX: Protein structure prediction with sparse NMR data
TOUCHSTONEX: Protein structure prediction with sparse NMR data
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DOI：
10.1002/prot.10499
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发表时间：
2003-11-01
期刊：
影响因子：
--
通讯作者：
Skolnick, J
中科院分区：
文献类型：
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作者：
Li, W;Zhang, Y;Skolnick, J
介绍了TOUCHSTONEX，一种折叠蛋白质的新方法，该方法使用来自核磁共振实验NOE（核Overhauser增强）数据的少量远程接触约束。该方法采用了一种新的基于晶格的蛋白质简化模型，明确表示c - α， c - β和侧链质量中心。力场由基于知识的术语组成，以产生类似蛋白质的行为，包括各种短程相互作用，氢键，以及单体，成对和多体远程相互作用。将接触约束作为noe特定的成对势纳入力场。我们使用一组125种不同二级结构类型和长度的蛋白质来评估该算法，最多174个残基。使用N/8模拟的远程侧链接触约束，其中N为残基数，108个蛋白质折叠到低于6.5埃的c - α -均方根偏差（RMSD）。所有125个蛋白（折叠和未折叠）的最低RMSD结构的平均RMSD为4.4埃。该算法还应用于三种蛋白质生成的有限实验NOE数据。使用很少的实验侧链接触约束，以及少量的侧链-主链和主链-主链接触约束，我们将所有三种蛋白质折叠成低至中等分辨率的结构。该算法可应用于核磁共振结构确定过程或其他可提供三级约束信息的实验方法，特别是在数据有限的结构确定早期。(C) 2003 Wiley-Liss, Inc。
TOUCHSTONEX, a new method for folding proteins that uses a small number of long-range contact restraints derived from NMR experimental NOE (nuclear Overhauser enhancement) data, is described. The method employs a new lattice-based, reduced model of proteins that explicitly represents C-alpha, C-beta, and the sidechain centers of mass. The force field consists of knowledge-based terms to produce protein-like behavior, including various short-range interactions, hydrogen bonding, and one-body, pairwise, and multibody long-range interactions. Contact restraints were incorporated into the force field as an NOE-specific pairwise potential. We evaluated the algorithm using a set of 125 proteins of various secondary structure types and lengths up to 174 residues. Using N/8 simulated, long-range sidechain contact restraints, where N is the number of residues, 108 proteins were folded to a C-alpha-root-mean-square deviation (RMSD) from native below 6.5 Angstrom. The average RMSD of the lowest RMSD structures for all 125 proteins (folded and unfolded) was 4.4 Angstrom. The algorithm was also applied to limited experimental NOE data generated for three proteins. Using very few experimental sidechain contact restraints, and a small number of sidechain-main chain and main chain-main chain contact restraints, we folded all three proteins to low-to-medium resolution structures. The algorithm can be applied to the NMR structure determination process or other experimental methods that can provide tertiary restraint information, especially in the early stage of structure determination, when only limited data are available. (C) 2003 Wiley-Liss, Inc.