Lepeshkevich Sergei V, Biziuk Sergey A, Lemeza Alexander M, Dzhagarov Boris M
National Academy of Sciences of Belarus, Minsk, Belarus.
Biochim Biophys Acta. 2011 Oct;1814(10):1279-88. doi: 10.1016/j.bbapap.2011.06.013. Epub 2011 Jul 8.
Bimolecular and germinate molecular oxygen (O(2)) rebinding to isolated α chains of human adult hemoglobin in solutions is analyzed. Multiple extended molecular dynamics (MD) simulations of the O(2) migration within the protein after dissociation are described. Computational modeling is exploited to identify hydrophobic pockets within the αchains and internal O(2) migration pathways associated with the experimentally observed ligand rebinding kinetics. To initiate dissociation, trajectories of the liganded protein are interrupted, the iron-dioxygen bond is broken, and the parameters of the iron-nitrogen bonds are simultaneously altered to produce a deoxyheme conformation. MD simulations provide 140 essentially independent trajectories (up to 25-ns long) of the O(2) migration in the protein. The time dependence of cavities occupancy, obtained by the MD simulations, and the kinetics of O(2) rebinding, measured by flash-photolysis techniques, allow us to obtain the kinetics of the entire O(2) migration process within the nanosecond time range and construct an explicit kinetic model of the O(2) migration and rebinding process. The amino acids that have the most pronounced effect on the ligand migration within the α chain matrix are predicted.
分析了双分子和萌发的分子氧（O₂）与溶液中成人血红蛋白分离的α链的重新结合。描述了离解后蛋白质内O₂迁移的多个扩展分子动力学（MD）模拟。利用计算模型来识别α链内的疏水口袋以及与实验观察到的配体重新结合动力学相关的内部O₂迁移途径。为了启动离解，打断配体化蛋白质的轨迹，打破铁-氧键，并同时改变铁-氮键的参数以产生脱氧血红素构象。MD模拟提供了蛋白质中O₂迁移的140条基本独立的轨迹（长达25纳秒）。通过MD模拟获得的空穴占有率的时间依赖性以及通过闪光光解技术测量的O₂重新结合动力学，使我们能够在纳秒时间范围内获得整个O₂迁移过程的动力学，并构建O₂迁移和重新结合过程的明确动力学模型。预测了对α链基质内配体迁移影响最显著的氨基酸。
