ANALYSIS OF ACCURACY AND IMPLICATIONS OF SIMPLE METHODS FOR PREDICTING SECONDARY STRUCTURE OF GLOBULAR PROTEINS
ANALYSIS OF ACCURACY AND IMPLICATIONS OF SIMPLE METHODS FOR PREDICTING SECONDARY STRUCTURE OF GLOBULAR PROTEINS
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DOI：
10.1016/0022-2836(78)90297-8
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发表时间：
1978-01-01
影响因子：
5.6
通讯作者：
ROBSON, B
中科院分区：
文献类型：
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作者：
GARNIER, J;OSGUTHORPE, DJ;ROBSON, B
一个有兴趣开发蛋白质二级结构预测方法理论的实验室与一个有兴趣应用和比较这些方法的实验室之间的合作，导致了一个简单的预测算法的开发。四态预测，其中每个残基被明确地指定为α-β的1个构象状态。螺旋，延伸链，反向转弯或卷曲，预测49%的残基状态正确（在26个蛋白质的样品）时，不考虑整体螺旋和延伸链的内容。当考虑到通过X射线晶体学观察到的螺旋、延伸链、反转和卷曲的相对丰度时，可以使用每个蛋白质和构象类型的单个常数来使预测偏置。当以这种方式优化预测时，所有残基状态的63%被明确且正确地分配。通过分析所需偏差的性质，蛋白质可以分为富含螺旋的类型、富含折叠的类型等，如果蛋白质的类型可以通过圆二色性近似确定，则可以在不考虑X射线结构的情况下正确预测57%的残基状态。如果不采用圆二色性，而是进行初步预测来评估蛋白质类型，则可以获得可比的预测。这里引用的数字取决于用于评估准确性的方法，该算法至少与以相同方式评估的报告预测方法一样好，并且通常上级。还探讨了通过使用来自疏水三联体和同源序列的额外信息来进一步增强预测的方法。疏水三联体信息并不能显著提高预测能力，这些信息可能被蛋白质在下一个折叠阶段使用。同源序列的使用似乎是非常有前途的。这些结果在蛋白质折叠的影响进行了讨论。
Cooperation between a laboratory interested in developing the theory for protein secondary structure prediction methods and a laboratory interested in applying and comparing such methods has led to the development of a simple predictive algorithm. Four-state predictions, in which each residue is unambiguously assigned 1 conformational state of .alpha.-helix, extended chain, reverse turn or coil, predict 49% of residue states correctly (in a sample of 26 proteins) when the overall helix and extended-chain content is not taken into account. When the relative abundances of helix, extended chain, reverse turn and coil observed by X-ray crystallography are taken into account, a single constant for each protein and type of conformation can be used to bias the prediction. When predictions are optimized in this way, 63% of all residue states are unambiguously and correctly assigned. By analyzing the nature of the bias required, proteins can be classified into helix-rich types, pleated-sheet-rich types and so on. If the type of protein can be determined even approximately by circular dichroism, 57% of residue states can be correctly predicted without taking into account the X-ray structure. Comparable predictions can be obtained if, instead of circular dichroism, preliminary predictions are made to assess the protein type. The numbers quoted here depend on the method used to assess accuracy, and the algorithm is at least as good as, and usually superior to, the reported prediction methods assessed in the same way. Ways of further enhancing predictions by the use of additional information from hydrophobic triplets and homologous sequences are also explored. Hydrophobic triplet information does not significantly improve predictive power and this information is probably used by proteins in the next stage of folding. The use of homologous sequences appears to be very promising. The implication of these results in protein folding is discussed.