RECOGNIZING NATIVE FOLDS BY THE ARRANGEMENT OF HYDROPHOBIC AND POLAR RESIDUES
RECOGNIZING NATIVE FOLDS BY THE ARRANGEMENT OF HYDROPHOBIC AND POLAR RESIDUES
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DOI：
10.1006/jmbi.1995.0529
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发表时间：
1995-10-06
影响因子：
5.6
通讯作者：
LEVITT, M
中科院分区：
文献类型：
--
作者：
HUANG, ES;SUBBIAH, S;LEVITT, M
从头算蛋白质折叠问题的核心是能量函数的发展，对于该能量函数，正确的天然结构具有比所有其他构象更低的能量。现有的平均力潜力通常广泛依赖于数据库导出的接触频率或三维结构信息的知识，以便成功地解决从一组诱饵骨架构象中识别给定序列的天然折叠的问题。这些基于知识的潜力是否需要使用详细的统计信息或复杂的分析来实现折叠识别中观察到的成功程度？在这里，我们引入了一种新颖的成对能量函数，该函数枚举疏水残基之间的接触，同时通过这些疏水残基周围的残基总数对它们的总和进行加权。因此，它有效地选择了具有埋藏完整核心所需结构特征的紧凑折叠。这种方法代表了使用成对项的进步，成对项的相互作用能量独立于蛋白质中的位置，并且极大地提高了能量函数的辨别能力。我们的结果表明，195 个代表性天然折叠中的 85% 被正确识别。29 个例外是亲脂性蛋白质、具有辅基或二硫键的小蛋白质以及寡聚蛋白质。总的来说，我们的方法将自然折叠与错误折叠分开的幅度（以标准差单位测量）比之前更复杂的方法所证明的要大。通过我们的新颖评分方案评估，疏水性和极性残基的单独排列在识别一般天然折叠方面出人意料地有效。令人惊讶的是，疏水性和极性残基的简单二元模式显然选择了给定的独特折叠拓扑。 (C) 1995 学术出版社有限公司
Central to the ab initio protein folding problem is the development of an energy function for which the correct native structure has a lower energy than all other conformations. Existing potentials of mean force typically rely extensively on database-derived contact frequencies or knowledge of three-dimensional structural information in order to be successful in the problem of recognizing the native fold for a given sequence from a set of decoy backbone conformations. Is the detailed statistical information or sophisticated analysis used by these knowledge-based potentials needed to achieve the observed degree of success in fold recognition? Here we introduce a novel pairwise energy function that enumerates contacts between hydrophobic residues while weighting their sum by the total number of residues surrounding these hydrophobic residues. Thus it effectively selects compact folds with the desired structural feature of a buried, intact core. This approach represents an advance over using pairwise terms whose energies of interaction that are independent of the position in the protein and greatly improves the discrimination capability of an energy function. Our results show that 85% of a set of 195 representative native folds were recognized correctly The 29 exceptions were lipophilic proteins, small proteins with prosthetic groups or disulfide bonds, and oligomeric proteins. Overall, our method separates the native fold from incorrect folds by a larger margin (measured in standard deviation units) than has been previously demonstrated by more sophisticated methods. The arrangement of hydrophobic and polar residues alone as evaluated by our novel scoring scheme, is unexpectedly effective at recognizing native folds in general. It is surprising that a simple binary pattern of hydrophobic and polar residues apparently selects a given unique fold topology. (C) 1995 Academic Press Limited