Ab initio fold prediction of small helical proteins using distance geometry and knowledge-based scoring functions
Ab initio fold prediction of small helical proteins using distance geometry and knowledge-based scoring functions
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DOI：
10.1006/jmbi.1999.2861
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发表时间：
1999-07-02
影响因子：
5.6
通讯作者：
Ponder, JW
中科院分区：
文献类型：
--
作者：
Huang, ES;Samudrala, R;Ponder, JW
从蛋白质一级序列预测蛋白质三级结构的问题可以分解为两个子问题：可能折叠的文库的生成；给定文库的最佳折叠的MD指定。基于具有良好采样特性的随机成对度量化的距离几何程序被用来为11个小螺旋蛋白质中的每一个生成一个包含500个可能结构的库。距离几何的输入由几组限制条件组成，以强制执行预测的螺旋二级结构和所有对螺旋上预测的接触残基之间的5到11埃的一般范围。对于每一个11.Target，所得到的文库包含的结构与原生结构相比具有较低的RMSD。与紧凑褶皱的随机抽样相比，近原生抽样至少提高了三个数量级。用全原子距离依赖函数、残基对势和疏水性函数的组合对所有文库成员进行评分。在11个案例中，排名最好的6个被认为是接近本地的。每个文库也被简化为最终的从头算预测，通过对全套500个结构中排名最好的50个结构执行一致距离几何运算。普遍的结果质量普遍较高，在原生褶皱的6.5埃范围内产生了6个预测。这些有利的预测与RMSD和评分功能之间的相关性最高的预测相对应。所报告的方法的优点是其极其简单，而且有可能纳入其他类型的结构限制。(C)1999年学术出版社。
The problem of protein tertiary structure prediction from primary sequence can be separated into two subproblems: generation of a library of possible folds;md specification of a best fold given the library. A distance geometry procedure based on random pairwise metrization with good sampling properties was used to generate a library of 500 possible structures for each of 11 small helical proteins. The input to distance geometry consisted of sets of restraints to enforce predicted helical secondary structure and a generic range of 5 to 11 Angstrom between predicted contact residues on all pairs of helices. For each of the 11. targets, the resulting library contained structures with low RMSD versus the native structure. Near-native sampling was enhanced by at least three orders of magnitude compared to a random sampling of compact folds. All library members were scored with a combination of an all-atom distance-dependent function, a residue pair-potential, and a hydrophobicity function. In six of the 11 cases, the best-ranking fold was considered to be near native. Each library was also reduced to a final ab initio prediction via consensus distance geometry performed over the 50 best-ranking structures from the full set of 500. The consensus results were of generally higher quality, yielding six predictions within 6.5 Angstrom of the native fold. These favorable predictions corresponded to those for which the correlation between the RMSD and the scoring function were highest. The advantage of the reported methodology is its extreme simplicity and potential for including other types of structural restraints. (C) 1999 Academic Press.