Departamento de Química Inorgánica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina.
Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE-CONICET), C1428EGA, Buenos Aires, Argentina.
Chemphyschem. 2019 Oct 2;20(19):2451-2460. doi: 10.1002/cphc.201900589. Epub 2019 Aug 14.
Computer simulation studies of the molecular basis for ligand migration in proteins allow the description of key events such as the transition between docking sites, displacement of existing ligands and solvent molecules, and open/closure of specific "gates", among others. In heme proteins, ligand migration from the solvent to the active site preludes the binding to the heme iron and triggers different functions. In this work, molecular dynamics simulations, a Markov State Model of migration and empirical kinetic equations are combined to study the migration of O and NO in two truncated hemoglobins of Mycobacterium tuberculosis (Mt-TrHbN and Mt-TrHbO). For Mt-TrHbN, we show that the difference in the association constant in the oxy and deoxy states relies mainly in the displacement of water molecules anchored in the distal cavity in the deoxy form. The results here provide a valuable approach to study ligand migration in globins.
计算机模拟研究蛋白质中配体迁移的分子基础，可以描述关键事件，如对接位点之间的转变、现有配体和溶剂分子的位移，以及特定“门”的开启/关闭等。在血红素蛋白中，配体从溶剂到活性部位的迁移先于与血红素铁的结合，并引发不同的功能。在这项工作中，我们将分子动力学模拟、迁移的马尔可夫状态模型和经验动力学方程相结合，研究了结核分枝杆菌两种截断血红蛋白（Mt-TrHbN 和 Mt-TrHbO）中 O 和 NO 的迁移。对于 Mt-TrHbN，我们表明氧合和脱氧状态下的结合常数的差异主要依赖于在脱氧形式中锚定在远端腔中的水分子的位移。这里的结果为研究球蛋白中的配体迁移提供了一种有价值的方法。
