Identification of high affinity fatty acid binding sites on human serum albumin by MM-PBSA method
Identification of high affinity fatty acid binding sites on human serum albumin by MM-PBSA method
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DOI：
10.1529/biophysj.107.111377
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Amisaki, Takashi
中科院分区：
文献类型：
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作者：
Fujiwara, Shin-Ichi;Amisaki, Takashi
人血清白蛋白（HSA）有7个常见的脂肪酸（FA）结合位点。在这项研究中，我们使用分子力学Poisson-Boltzmann表面积方法来确定高亲和力的FA结合位点的结合自由能。利用分子动力学模拟构建的多个HSA-FA（肉豆蔻酸酯、棕榈酸酯）复合物模型，在分子力学Poisson-Boltzmann表面积中采用“三轨线法”和“单轨线法”两种方法.前者比后者精确度低，但可能更准确，因为它包括结合后构象变化的影响，用于对高和低亲和力位点进行分类。结果，位点2、4和5被鉴定为两种FA的高亲和力位点。后一种方法是精确的，因为能量是从HSA-FA复合物的相同轨迹的快照计算的，用于比较这些位点的结合自由能的大小。数量级为5>4>2，与其他人先前发表的数量级相同。以这种方式，两种方法的组合被有效地用于鉴定高亲和力位点。因此，这项研究提供了一个深入的定量鉴定高亲和力FA结合位点的HSA。
Human serum albumin (HSA) has seven common fatty acid ( FA) binding sites. In this study, we used the molecular mechanics Poisson-Boltzmann surface area method to identify high affinity FA binding sites on HSA in terms of binding free energy. Using multiple HSA-FA (myristate, palmitate) complex models constructed by molecular dynamics simulations, two methods were performed in molecular mechanics Poisson-Boltzmann surface area, the "three-trajectory method'' and the "single-trajectory method''. The former, which is less precise than the latter but may be more accurate as it includes the effects of conformational change upon binding, was used to classify high and low affinity sites. As a result, Sites 2, 4, and 5 were identified as high affinity sites for both FAs. The latter method, which is precise because energies are calculated from snapshots of the same trajectory for HSA-FAcomplex, was performed to compare the magnitude of binding free energy for these sites. The order of magnitude was 5>4>2, identical to that of a previous publication by others. In this way, a combination of the two methods was effectively used to identify high affinity sites. This study therefore provides an insight into the quantitative identification of high affinity FA binding sites on HSA.