Sequence determinants of protein folding rates: Positive correlation between contact energy and contact range indicates selection for fast folding
Sequence determinants of protein folding rates: Positive correlation between contact energy and contact range indicates selection for fast folding
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DOI：
10.1002/prot.24118
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发表时间：
2012-08-01
影响因子：
2.9
通讯作者：
Luis Velasco, Jose
中科院分区：
文献类型：
--
作者：
Bastolla, Ugo;Bruscolini, Pierpaolo;Luis Velasco, Jose
与对蛋白质折叠速率的结构决定因素的深入研究相比，有利于快速折叠的序列特征很少受到关注。在这里，我们调查这个问题，使用简单的模型的蛋白质折叠和蛋白质数据库（PDB）的统计分析。Plotkin及其同事的平均场模型预测，折叠速率会因序列沿着短距离处强于平均值的相互作用而加速。我们使用Finkelstein蛋白质折叠模型证实了这一预测，该模型解释了聚合物熵的现实特征。然后我们在PDB上测试了这个预测。我们发现，本地的相互作用是最强的接触范围l = 8。然而，由于短距离接触件倾向于暴露并且它们经常以错误折叠的结构形成，所以对折叠稳定性的选择倾向于使它们不那么有吸引力，即，稳定性和动力学可能具有对比的要求。使用最近提出的模型，我们预测的接触范围和接触能量之间的关系的基础上埋和接触频率。与此预测的偏差诱导接触范围和接触能量之间的正相关性，即，对于2/3的蛋白质，短程接触比预期的更强。这种相关性随着绝对接触顺序（ACO）而增加，正如预期的那样，如果由于大ACO而倾向于缓慢折叠的蛋白质受到有利于快速折叠的序列特征的更强选择。我们的研究结果表明，快速折叠的选择压力是可检测的PDB中的蛋白质，特别是那些与大的接触顺序的三分之一。Proteins 2012;（c）2012 Wiley Periodicals，Inc.
In comparison with intense investigation of the structural determinants of protein folding rates, the sequence features favoring fast folding have received little attention. Here, we investigate this subject using simple models of protein folding and a statistical analysis of the Protein Data Bank (PDB). The mean-field model by Plotkin and coworkers predicts that the folding rate is accelerated by stronger-than-average interactions at short distance along the sequence. We confirmed this prediction using the Finkelstein model of protein folding, which accounts for realistic features of polymer entropy. We then tested this prediction on the PDB. We found that native interactions are strongest at contact range l = 8. However, since short range contacts tend to be exposed and they are frequently formed in misfolded structures, selection for folding stability tends to make them less attractive, that is, stability and kinetics may have contrasting requirements. Using a recently proposed model, we predicted the relationship between contact range and contact energy based on buriedness and contact frequency. Deviations from this prediction induce a positive correlation between contact range and contact energy, that is, short range contacts are stronger than expected, for 2/3 of the proteins. This correlation increases with the absolute contact order (ACO), as expected if proteins that tend to fold slowly due to large ACO are subject to stronger selection for sequence features favoring fast folding. Our results suggest that the selective pressure for fast folding is detectable only for one third of the proteins in the PDB, in particular those with large contact order. Proteins 2012; (c) 2012 Wiley Periodicals, Inc.