Free-Energy Function for Discriminating the Native Fold of a Protein from Misfolded Decoys
Free-Energy Function for Discriminating the Native Fold of a Protein from Misfolded Decoys
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用于区分蛋白质天然折叠和错误折叠诱饵的自由能函数
DOI：
10.1002/prot.23036
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发表时间：
2011
影响因子：
2.9
通讯作者：
M.Kinoshita
中科院分区：
文献类型：
--
作者：
S.Yasuda;T.Yoshidome;Y.Harano;E.Roth;H.Oshima;K.Oda;Y.Sugita;M.Ikeguchi;M.Kinoshita
在这项研究中，自由能函数（FEF）用于区分蛋白质的天然折叠与错误折叠的诱饵进行了研究。它是一个基于物理的函数，使用全原子模型，包括水合熵（HE）和总脱水惩罚（TDP）。HE是使用一个混合动力机械理论应用于水的分子模型和形态测量方法计算的。能量分量以简单的方式被适当地考虑为TDP。的FEF，已进行了118个蛋白质的代表性诱饵集的仔细测试的结果的基础上，我们表明，它的性能是明显优于任何其他功能的上级。对于从核磁共振实验获得的天然结构（NS）的候选模型，FEF在模型之间变化很大，但是我们可以找到FEF变得低于任何诱饵结构的模型或模型。在考虑从蛋白质复合物中分离的蛋白质并且复合物中的结构被用作分离的蛋白质的模型NS而没有任何变化的情况下，或者在蛋白质的末端侧的部分被去除并且由于去除而损失的二级结构的百分比显著高的情况下，诱饵集不适合于自由能或势函数的测试。由于这些发现是可能的，我们可以假设，我们的FEF准确地捕捉到真正的NS的功能。Proteins 2011; © 2011 Wiley利斯，Inc.
In this study, free‐energy function (FEF) for discriminating the native fold of a protein from misfolded decoys was investigated. It is a physics‐based function using an all‐atom model, which comprises the hydration entropy (HE) and the total dehydration penalty (TDP). The HE is calculated using a hybrid of a statistical–mechanical theory applied to a molecular model for water and the morphometric approach. The energetic component is suitably taken into account in a simple manner as the TDP. On the basis of the results from a careful test of the FEF, which have been performed for 118 proteins in representative decoy sets, we show that its performance is distinctly superior to that of any other function. The FEF varies largely from model to model for the candidate models for the native structure (NS) obtained from nuclear magnetic resonance experiments, but we can find models or a model for which the FEF becomes lower than for any of the decoy structures. A decoy set is not suited to the test of a free‐energy or potential function in cases where a protein isolated from a protein complex is considered and the structure in the complex is used as the model NS of the isolated protein without any change or where portions of the terminus sides of a protein are removed and the percentage of the secondary structures lost due to the removal is significantly high. As these findings are made possible, we can assume that our FEF precisely captures the features of the true NS. Proteins 2011; © 2011 Wiley‐Liss, Inc.