Atomic-Level Characterization of the Structural Dynamics of Proteins
Atomic-Level Characterization of the Structural Dynamics of Proteins
复制标题
DOI：
10.1126/science.1187409
复制
发表时间：
2010-10-15
期刊：
影响因子：
56.9
通讯作者：
Wriggers, Willy
中科院分区：
文献类型：
--
作者：
Shaw, David E.;Maragakis, Paul;Wriggers, Willy
分子动力学（MD）模拟被广泛用于研究蛋白质运动的原子水平的细节，但他们一直局限于时间尺度短于许多生物学关键的构象变化。我们研究了蛋白质动力学的两个基本过程-蛋白质折叠和折叠状态内的构象变化-通过在专用机器上进行的极长的全原子MD模拟。WW蛋白质结构域的平衡模拟捕获了多个折叠和展开事件，这些事件始终遵循一个明确的折叠途径;蛋白质组成子结构的单独模拟揭示了这一途径的可能决定因素。折叠蛋白质BPTI的1毫秒模拟揭示了少量结构上不同的构象状态，其可逆的相互转换比这些状态内的局部弛豫慢1000倍以上。
Molecular dynamics (MD) simulations are widely used to study protein motions at an atomic level of detail, but they have been limited to time scales shorter than those of many biologically critical conformational changes. We examined two fundamental processes in protein dynamics-protein folding and conformational change within the folded state-by means of extremely long all-atom MD simulations conducted on a special-purpose machine. Equilibrium simulations of a WW protein domain captured multiple folding and unfolding events that consistently follow a well-defined folding pathway; separate simulations of the protein's constituent substructures shed light on possible determinants of this pathway. A 1-millisecond simulation of the folded protein BPTI reveals a small number of structurally distinct conformational states whose reversible interconversion is slower than local relaxations within those states by a factor of more than 1000.