Improved pKa Prediction: Combining Empirical and Semimicroscopic Methods
Improved pKa Prediction: Combining Empirical and Semimicroscopic Methods
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DOI：
10.1002/jcc.20999
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发表时间：
2008-11-30
影响因子：
3
通讯作者：
Knapp, E. W.
中科院分区：
文献类型：
--
作者：
Kieseritzky, Gernot;Knapp, E. W.
用三种不同的方法计算了15种蛋白质的171个已知的pK（a）值，并比较了计算值与实验值的均方根偏差（RMSD）。一种方法是基于包括构象柔性的蛋白质的连续静电模型（KBPLUS）。其他的是经验方法与PROPKA部署物理激励的能量项与可调参数和PKAcal使用经验函数没有物理基础。PROPKA以最高的总体准确度再现了pK（a）值。然而，将数据集区分为弱位移和强位移的实验pK（a）值，我们发现，如果pK（a）值弱位移，则PROPKA的准确性更好，但对于更强位移的值，PROPKA的准确性与KBPLUS的准确性相同。另一方面，PKAcal以与PROPKA相同的准确度再现了强烈移位的pK（a）值，但弱移位的值。我们测试了不同的共识方法，结合所有三种方法的数据，以找到最准确的pK（a）预测的一般程序。在大多数情况下，我们发现共识方法比单独使用任何一种方法都能更准确地再现实验数据。(C)2008 Wiley Periodicals，Inc. J Comput Chem 29：2575-2581，2008
Using three different methods we tried to compute 171 experimentally known pK(a) values of ionizable residues front 15 different proteins and compared the accuracies of computed pK(a) values in terms of the root mean square deviation (RMSD) from experiment. One method is based on a continuum electrostatic model of the protein including conformational flexibility (KBPLUS). The others are empirical approaches with PROPKA deploying physically motivated energy terms with adjustable parameters and PKAcal using an empirical function with no physical basis. PROPKA reproduced the pK(a) values with highest overall accuracy. Differentiating the data set into weakly and strongly shifted experimental pK(a) values, however, we found that PROPKA's accuracy is better if the pK(a) values are weakly shifted but on equal footing with that of KBPLUS for more strongly shifted values. On the other hand, PKAcal reproduces strongly shifted pK(a) values badly but weakly shifted values with the same accuracy as PROPKA. We tested different consensus approaches Combining data front all three methods to find a general procedure for most accurate pK(a) predictions. In most of the cases we found that the consensus approach reproduced experimental data with better accuracy than any of the individual methods alone. (C) 2008 Wiley Periodicals, Inc. J Comput Chem 29: 2575-2581, 2008