Molecular dynamics study of conformational changes in human serum albumin by binding of fatty acids
Molecular dynamics study of conformational changes in human serum albumin by binding of fatty acids
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DOI：
10.1002/prot.21053
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发表时间：
2006-08-15
影响因子：
2.9
通讯作者：
Amisaki, Takashi
中科院分区：
文献类型：
--
作者：
Fujiwara, Shin-ichi;Amisaki, Takashi
人血清白蛋白（HSA）在正常生理条件下与脂肪酸结合。迄今为止，很少有公开的信息，在水溶液中的HSA-脂肪酸复合物的三级结构。在本研究中，我们使用分子动力学（MD）模拟来阐明可能的结构变化的HSA所带来的结合脂肪酸。分子动力学计算的未配体HSA和HSA-脂肪酸复合物模型都是基于X-射线晶体结构构建的。在HSA-脂肪酸复合物模型中结合了五种肉豆蔻酸酯（MYR）。在本MD研究中，由MYR分子结合引起的结构域I和III的运动增加了HSA的回转半径。根均方波动从MD模拟显示，在药物结合位点I，可以调节药物结合亲和力的特定氨基酸的原子波动增加的MYR分子的结合。主要的内部运动，其特征在于前三个主成分，观察到主要在域I和III的轨迹数据的主成分分析。在HSA-MYR复合物中，投射在未配体的HSA第一主成分上的定向运动是保守的，是频率较高的第三主方向运动。然而，在未配体的HSA中的第三主方向运动在HSA-MYR复合物中以较低的频率变为第一主方向运动。因此，本MD研究提供了由脂肪酸的结合引起的HSA的可能的构象变化的见解。
Human serum albumin (HSA) binds with fatty acids under normal physiologic conditions. To date, there is little published information on the tertiary structure of HSA-fatty acid complex in aqueous solution. In the present study, we used molecular dynamics (MD) simulations to elucidate possible structural changes of HSA brought about by the binding of fatty acids. Both unliganded HSA and HSA-fatty acid complex models for MD calculations were constructed based on the X-ray crystal structures. Five myristates (MYRs) were bound in the HSA-fatty acid complex model. In the present MD study, the motion of domains I and III caused by the binding of MYR molecules increased the radius of gyration of HSA. Root-mean-square fluctuations from the MD simulations revealed that the atomic fluctuations of the specific amino acids at drug-binding site I that can regulate the drug-binding affinity were increased by the binding of MYR molecules. Primary internal motions, characterized by the first three principal components, were observed mainly at domains I and III in the principal component analysis for trajectory data. The directional motion projected on the first principal component of unliganded HSA was conserved in HSA-MYR complex as the third principal directional motion with higher frequency. However, the third principal directional motion in unliganded HSA turned into the first principal directional motion with lower frequency in the HSA-MYR complex. Thus, the present MD study provides insights into the possible conformational changes of HSA caused by the binding of fatty acids.