Computational studies on imidazole heme conformations
Computational studies on imidazole heme conformations
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DOI：
10.1007/s00775-005-0642-8
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发表时间：
2005-06-01
影响因子：
3
通讯作者：
Knapp, EW
中科院分区：
文献类型：
--
作者：
Galstyan, AS;Zariç, SD;Knapp, EW
密度泛函理论计算血红素离子化丙酸基团，轴向协调与两个咪唑，进行了不同的相互取向的咪唑平面。通过求解泊松方程，考虑了水或蛋白质对连续介质的环境影响。在真空中，优化的几何形状产生咪唑-血红素构象，其中咪唑的NH基团朝向血红素丙酸基团，与来自血红素蛋白质的晶体结构的数据一致。蛋白质中轴向连接咪唑分子相互取向的构象自由能依赖性（10）水（λ = 80）环境证实了真空结果，尽管咪唑配体的优选取向和180度相反取向之间的能量差从真空中的3.84千卡/摩尔降低到2.35和2.40千卡/摩尔，mol/L。两个主要因素决定了咪唑的取向：（1）丙酸基团与咪唑的极性NH基团的直接分子内静电相互作用和（2）咪唑-血红素复合物的总偶极矩与反应场的静电相互作用。在真空中，只有第一种类型的相互作用是存在的，而在介电介质中，后者的效果变得具有竞争力，在高介电常数，导致取向偏好的减少。有趣的是，轴向连接到血红素的咪唑的取向偏好变得更加明显，如果带负电荷的丙酸盐被反电荷，模仿盐桥或质子化的丙酸盐中和。
Density functional theory computations of heme with ionized propionic acid groups, axially coordinated with two imidazoles, were performed for different mutual orientations of the imidazole planes. Environmental influences from water or protein were considered with a continuum dielectric medium by solving the Poisson equation. In vacuum, optimized geometries yielded imidazole - heme conformations where the NH groups of imidazoles are oriented toward the heme propionic groups in agreement with data from crystal structures of heme proteins. Conformational free-energy dependencies of the mutual orientation of axially ligated imidazoles calculated in protein ( epsilon = 10) and water (epsilon = 80) environments confirmed the vacuum results, albeit the energy difference between the preferred and the 180 degrees opposite orientations of the imidazole ligand decreased from 3.84 kcal/mol in vacuum to 2.35 and 2.40 kcal/mol in protein and water, respectively. Two main factors determine the imidazole orientation: ( 1) the direct intramolecular electrostatic interactions of propionic groups with the polar NH groups of imidazole and ( 2) the electrostatic interaction of the total dipole moment of the imidazole - heme complex with the reaction field. In vacuum, only the first type of interaction is present, while in a dielectric medium the latter effect becomes competitive at high dielectric constant, resulting in a decrease of the orientational preference. Interestingly, the orientational preference of the imidazole axially ligated to heme becomes even more pronounced, if the negatively charged propionates are neutralized by counter charges that mimic salt bridges or protonation of the propionates.