Bass M B, Hopkins D F, Jaquysh W A, Ornstein R L
Molecular Science Research Center, Pacific Northwest Laboratory, Richland, Washington 99352.
Proteins. 1992 Mar;12(3):266-77. doi: 10.1002/prot.340120305.
An automated method for the optimal placement of polar hydrogens in a protein structure is described. This method treats the polar, side chain hydrogens of lysine, serine, threonine, and tyrosine and the amino terminus of a protein. The program, called NETWORK, divides the potential hydrogen-bonding pairs of a protein into groups of interacting donors and acceptors. A search is conducted on each of the local groups to find an arrangement which forms the most hydrogen bonds. If two or more arrangements have the same number of hydrogen bonds, the arrangement with the shortest set of hydrogen bonds is selected. The polar hydrogens of the histidyl side chain are specifically treated, and the ionization state of this residue is allowed to change, if this change results in additional hydrogen bonds for the local group. The program will accept Protein Data Bank as well as Biosym-format coordinate files. Input and output routines can be easily modified to accept other coordinate file formats. The predictions from this method are compared to known hydrogen positions for bovine pancreatic trypsin inhibitor, insulin, RNase-A, and trypsin for which the neutron diffraction structures have been determined. The usefulness of this program is further demonstrated by a comparison of molecular dynamics simulations for the enzyme cytochrome P-450cam with and without using NETWORK.
本文描述了一种用于在蛋白质结构中优化放置极性氢原子的自动化方法。该方法处理赖氨酸、丝氨酸、苏氨酸和酪氨酸的极性侧链氢原子以及蛋白质的氨基末端。这个名为NETWORK的程序将蛋白质中潜在的氢键对分为相互作用的供体和受体组。对每个局部组进行搜索，以找到形成最多氢键的排列方式。如果两种或更多种排列方式具有相同数量的氢键，则选择氢键最短的排列方式。组氨酸侧链的极性氢原子会被专门处理，并且如果这种变化会为局部组带来额外的氢键，则允许该残基的电离状态发生变化。该程序将接受蛋白质数据库以及Biosym格式的坐标文件。输入和输出例程可以很容易地修改以接受其他坐标文件格式。将该方法的预测结果与已确定中子衍射结构的牛胰蛋白酶抑制剂、胰岛素、核糖核酸酶A和胰蛋白酶的已知氢原子位置进行了比较。通过对使用和不使用NETWORK的细胞色素P - 450cam酶的分子动力学模拟进行比较，进一步证明了该程序的实用性。
