Folding simulations of Trp-cage mini protein in explicit solvent using biasing potential replica-exchange molecular dynamics simulations
Folding simulations of Trp-cage mini protein in explicit solvent using biasing potential replica-exchange molecular dynamics simulations
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DOI：
10.1002/prot.22359
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发表时间：
2009-08-01
影响因子：
2.9
通讯作者：
Zacharias, Martin
中科院分区：
文献类型：
--
作者：
Kannan, Srinivasaraghavan;Zacharias, Martin
复制交换分子动力学（RexMD）模拟经常用于研究肽和蛋白质的结构形成和动力学。然而，标准温度RexMD的一个显著缺点是，随着系统尺寸的增加，复制品数量迅速增加，以覆盖期望的温度范围。最近开发的Hamiltonian RexMD方法已被用来研究折叠的色氨酸笼蛋白。它采用的偏置电位，降低了骨干二面角的障碍，并促进肽骨架转换沿着副本坐标。在两个独立的应用程序的偏置电位RexMD方法，包括明确的溶剂，并从一个完全展开的结构，近天然构象的形成后，观察到30-40 ns的模拟时间。在最后的模拟阶段的构象代表人口最多的集群有一个骨干均方根偏差类似于1.3埃的实验结构。这是实现了一个非常适度的数量为五个复制品，使其非常适合肽和蛋白质折叠和细化研究，包括明确的溶剂。相比之下，在五个独立的连续70 ns的分子动力学模拟坍塌状态的形成，但没有近原生结构的形成观察。模拟预测了一个很大程度上崩溃的状态，具有显着的螺旋倾向的螺旋结构域的Trp-笼蛋白已经在展开状态。氢键桥接水分子被确定，可以发挥积极的作用，通过稳定的螺旋结构域的安排相对于其余的链已经在中间状态的蛋白质。
Replica exchange molecular dynamics (RexMD) simulations are frequently used for studying structure formation and dynamics of peptides and proteins. A significant drawback of standard temperature RexMD is, however, the rapid increase of the replica number with increasing system size to cover a desired temperature range. A recently developed Hamiltonian RexMD method has been used to study folding of the Trp-cage protein. It employs a biasing potential that lowers the backbone dihedral barriers and promotes peptide backbone transitions along the replica coordinate. In two independent applications of the biasing potential RexMD method including explicit solvent and starting from a completely unfolded structure the formation of near-native conformations was observed after 30-40 ns simulation time. The conformation representing the most populated cluster at the final simulation stage had a backbone root mean square deviation of similar to 1.3 angstrom from the experimental structure. This was achieved with a very modest number of five replicas making it well suited for peptide and protein folding and refinement studies including explicit solvent. In contrast, during five independent continuous 70 ns molecular dynamics simulations formation of collapsed states but no near native structure formation was observed. The simulations predict a largely collapsed state with a significant helical propensity for the helical domain of the Trp-cage protein already in the unfolded state. Hydrogen bonded bridging water molecules were identified that could play an active role by stabilizing the arrangement of the helical domain with respect to the rest of the chain already in intermediate states of the protein.