Energy embedding of trypsin inhibitor
Energy embedding of trypsin inhibitor
复制标题
胰蛋白酶抑制剂的能量嵌入
DOI：
10.1002/bip.360211002
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发表时间：
1982
期刊：
影响因子：
2.9
通讯作者：
G. Crippen
中科院分区：
文献类型：
--
作者：
G. Crippen
能量嵌入最近已被证明是一个有用的扩展的距离几何方法的构象计算的情况下，非常小的分子和简单的能量函数。当分子为小分子蛋白质-牛胰蛋白酶抑制剂，能量函数为复杂的Oobatake-Crippen残基-残基势时，本文研究了能量嵌入法定位满足弱和强几何约束的低能构象的能力.仅使用势函数，该算法得到能量低于天然构象的能量的结构，但与天然构象几乎没有相似之处。借助于许多几何约束，例如预先形成的二级结构片段，该算法再次找到能量优于天然构象的局部最小值，与仅使用标准距离几何和几何约束获得的值相比，这明显更接近原始值。因此，使用Oobatake-Crippen势函数的能量嵌入对寻找蛋白质的天然构象有重要帮助。然而，对胰蛋白酶抑制剂的发夹弯曲片段的额外试验证明了这种潜力在促进适当的二级结构方面的缺点。
Energy embedding has been shown recently to be a useful extension of the distance geometry approach to conformational calculations in the case of very small molecules and simple energy functions. This paper tests the ability of energy embedding to locate low energy conformations satisfying both weak and strong geometric constraints when the molecule is the small protein, bovine pancreatic trypsin inhibitor, and the energy function is the complicated Oobatake‐Crippen residue–residue potential. Using the potential function alone, the algorithm reaches a structure with energy lower than that of the native conformation, but with little resemblance to it. Aided by numerous geometric constraints, such as preformed secondary structure segments, the algorithm again finds a local minimum with energy better than that of the native, and with only 3.3 Å rms deviation from it. This is significantly closer to the native value than can be obtained using standard distance geometry and the geometric constraints alone. Thus, energy embedding using the Oobatake‐Crippen potential function is a significant help in finding native conformations of proteins. However, additional trials on a hairpin bend fragment of trypsin inhibitor demonstrate the potential's shortcomings in encouraging proper secondary structure.